Matini Zack- 1Cognitive Psychopharmacology Laboratory, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, ON, Canada
- 2Translational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- 3Biopsychology Section, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, ON, Canada
Addiction is considered to be a brain disease caused by chronic exposure to drugs. Sensitization of brain dopamine (DA) systems partly mediates this effect. Pathological gambling (PG) is considered to be a behavioral addiction. Therefore, PG may be caused by chronic exposure to gambling. Identifying a gambling-induced sensitization of DA systems would support this possibility. Gambling rewards evoke DA release. One episode of slot machine play shifts the DA response from reward delivery to onset of cues (spinning reels) for reward, in line with temporal difference learning principles. Thus, conditioned stimuli (CS) play a key role in DA responses to gambling. In primates, DA response to a CS is strongest when reward probability is 50%. Under this schedule the CS elicits an expectancy of reward but provides no information about whether it will occur on a given trial. During gambling, a 50% schedule should elicit maximal DA release. This closely matches reward frequency (46%) on a commercial slot machine. DA release can contribute to sensitization, especially for amphetamine. Chronic exposure to a CS that predicts reward 50% of the time could mimic this effect. We tested this hypothesis in three studies with rats. Animals received 15 × 45-min exposures to a CS that predicted reward with a probability of 0, 25, 50, 75, or 100%. The CS was a light; the reward was a 10% sucrose solution. After training, rats received a sensitizing regimen of five separate doses (1 mg/kg) of d-amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to a 90-min locomotor activity test. In all three studies the 50% group displayed greater activity than the other groups in response to both challenge doses. Effect sizes were modest but consistent, as reflected by a significant group × rank association (ϕ = 0.986, p = 0.025). Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine much like exposure to amphetamine itself.
faʻatomuaga
Addiction has been characterized as a brain disease caused by chronic exposure to drugs of abuse (Leshner, 1997). Neuroplasticity is thought to mediate the effects of such exposure (Nestler, 2001). Sensitization of brain dopamine (DA) systems is a form of neuroplasticity implicated in hyper-reactivity to conditioned stimuli (CS) for drugs, and compulsive drug seeking (Robinson ma Berridge, 2001). Sensitization has been operationally defined by increased DA release in response to a CS for reward and by increased locomotor response to pharmacological DA challenge (Robinson ma Berridge, 1993; Pierce ma Kalivas, 1997; Vanderschuren ma Kalivas, 2000). Although sensitization is only one of many brain changes linked with addiction (cf. Robbins ma Everitt, 1999; Koob ma Le Moal, 2008), changes in presynaptic dopamine release have been suggested to represent common neuroadaptations involved in addiction-based drug-seeking (e.g., relapse), in that drugs that induce locomotor sensitization to opiate (e.g., morphine) or stimulant challenge (e.g., amphetamine), also cause reinstatement of extinguished operant responses for heroin or cocaine self-administration—an animal model of relapse (Vanderschuren et al., 1999). Evidence that incentive sensitization (increased value of drug reward) is most pronounced after initial exposure to addictive drugs further suggests that sensitization may be involved in the early stages of addiction as well (Vanderschuren ma Pierce, 2010).
Pathological gambling (PG) has been described as a behavioral addiction and recently reclassified to the same category as substance dependence disorders in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (Frascella et al., 2010; A.P.A., 2013). This implies that PG may be caused by chronic exposure to gambling-like activity, that common mechanisms may mediate the effects of gambling and drug exposure (Zack ma Poulos, 2009; Leeman ma Potenza, 2012); ma o le faʻalogoina o ala o faiʻai DA atonu o se tasi o elemene taua o lenei faagasologa.
Clinical evidence indirectly supports this possibility: Using positron emission tomography (PET) Boileau and colleagues found that male PG subjects exhibit significantly greater striatal DA release in response to amphetamine (0.4 mg/kg) than healthy male controls (Boileau et al., 2013). Overall group differences were significant in the associative and somatosensory striatum. In the limbic striatum, which includes the nucleus accumbens, the groups did not differ. However, in PG subjects, DA release in the limbic striatum correlated directly with the severity of PG symptoms. These findings are consistent with sensitization of brain DA pathways in PG, but also suggest some important differences with human substance dependent individuals and with the classic animal model of amphetamine sensitization. Unlike PG subjects and animals exposed to low doses of amphetamine (cf. Robinson et al., 1982), humans with substance dependence consistently exhibit decreased DA release to a stimulant challenge (Volkow et al., 1997; Martinez et al., 2007), and evidence from animals suggests that this may reflect deficits in DA function during the initial stages of abstinence following binge patterns of substance abuse (Mateo et al., 2005). In studies where stimulant sensitization is demonstrated in animals, enhanced DA release is usually observed in the limbic striatum rather than the dorsal (associative, somatosensory) striatum (Vezina, 2004). However, cue-induced (i.e., conditioned) drug-seeking in animals repeatedly exposed to cocaine has been linked with enhanced DA release in the dorsal striatum, a result thought to indicate a more habitual form of motivated behavior (Ito et al., 2002). Thus, the overall elevation in DA release in dorsal regions in PG subjects may be related to habit-based (inflexible, routinized) reward seeking involving “a progression from ventral to more dorsal domains of the striatum” (Everitt ma Robbins, 2005, i. 1481), ae o le faʻamalologa faʻalagolago i le DA i le limbic striatum i nei mataupu e mafai ona sili atu ona vavalalata ma faʻaosofia lagona e pei ona masani ona faʻataʻitaʻiina i manu. O suʻesuʻega a le PET e le mafai ona faʻaalia pe o le DA hyper-reactivity o se vaega muamua o nei mataupu PG, o se taunuuga o le faʻaalia o taaloga faitupe, poʻo se taunuuga o se isi gaioiga atoa. Ina ia taliina lenei fesili, e tatau ona faʻaalia le faʻaalia o le faʻaalia e ala i le faʻaalia o taaloga faitupe i mataupu masani aʻo leʻi faʻaalia. E tula'i mai ai fesili po'o a vaega o taaloga faitupe e ono fa'atupu ai le fa'alogo.
Skinner noted that the variable schedule of reinforcement was fundamental to gambling’s allure (or at least its persistence) (Skinner, 1953). Betting behavior in a slot machine game conforms well to the basic principles of instrumental conditioning, as reflected by a prospective correlation between monetary payoff and bet size on consecutive spins (Tremblay et al., 2011). O le mea lea, o le fua faatatau fesuisuia'i o le tali atu e foliga mai o lo'o maua ai se fa'ata'ita'iga fa'aa'oa'oga fa'apitoa o taaloga faitupe masini slot.
Recent research with animals provides strong initial support for a causal effect of gambling exposure on sensitization. Singer and colleagues examined the effects of 55 1–h daily sessions of fixed (FR20) or variable (VR20) saccharin reinforcement in an operant lever-press paradigm on subsequent locomotor response to low dose (0.5 mg/kg) amphetamine in healthy male (Sprague Dawley) rats (Singer et al., 2012). Na latou manatu e faapea, afai o taaloga faitupe e taitai atu ai i lagona, o isumu e aafia i le faasologa fesuisuiai, lea e pei o taaloga faitupe, e tatau ona sili atu le tali atu i le amphetamine nai lo iole o loʻo faʻaalia i le taimi faatulagaina. E pei ona valoia, o le VR20 vaega na faʻaalia 50% sili atu locomotor tali i amphetamine nai lo le FR20 vaega. I se fa'atusatusaga, na fa'aalia e vaega fa'atusa le gaioioiga pe a mae'a le tui masima. O nei suʻesuʻega e faʻamaonia ai o le faʻaalia faifaipea i le fesuiaiga o le faʻamalosia e lava lea e faʻaosofia ai le hyper-reactivity i se luʻitau a le DA i manu soifua maloloina faʻasolosolo i taimi taʻitasi.
A number of questions arise from this result: First, to what extent does the perceived contingency—or lack thereof—between the operant response and its outcome mediate these effects? In learning terms, does this effect involve a “response-outcome expectancy,” or might a similar effect be seen in the absence of an operant response, i.e., “a stimulus-outcome expectancy” in a Pavlovian paradigm (cf. Bolles, 1972)? Lona lua, pe o le maualuga o le faʻalavelave i le va o le mea na tupu muamua (tali poʻo le faʻaosofia) ma lona taunuuga e aʻafia ai le maualuga o le lagona?
O le fesili lona lua e faatatau i le matafaioi o le le mautonu i le lagona. Mo se faʻataʻitaʻiga, pe o taʻaloga e matuaʻi faʻafuaseʻi lava lona iʻuga-e matua le mafaamatalaina-e sili atu le gafatia e faʻaosofia ai le lagona nai lo taaloga e faʻamalamalama manino ai le faigata o le manumalo ae le o se mea faʻafuaseʻi, e tusa lava pe maualalo le tau o le taui? O suʻesuʻega i le taimi nei na taliina ai nei fesili.
The experimental design was informed by a seminal study on reward expectancy and DA neuron response in monkeys (Fiorillo et al., 2003). O manu i lena suʻesuʻega na maua se taui sua (US) i lalo ole 0, 25, 50, 75, poʻo le 100% faʻasologa faʻasologa o fuainumera. O fa'atulagaga na fa'atulaga e le 1 o le 4 eseese CS (icons). O le 0% faʻasologa na tuʻuina atu taui i taimi uma e pei o le 100% faʻasologa, ae faʻaumatia le CS. O le sasaina o le fua o le DA neurons i le taimi o le va o le CS ma le tuʻuina atu a le US poʻo le le faia o le fua faʻalagolago lea. Na maua e le suʻesuʻega o le tali a le DA na faʻateleina o se galuega o le le mautonu o le tuʻuina atu o taui. O le mea lea, i lalo o le 100% faʻatulagaina o le CS na faʻaalia ai ni gaioiga laiti, i lalo o le 25 ma le 75% faʻatulagaina, na faʻaalia e le CS le tulaga faʻapitoa ma tutusa tutusa, ma i lalo o le 50% faʻasologa o le CS na faʻaalia ai le gaioiga sili. I tulaga ta'itasi, na fa'atupula'ia le fua fa'afana i le gasologa o le vaeluaga o le CS-US, o lona uiga, a'o latalata le fa'amoemoe e fua mai.
O nei suʻesuʻega o loʻo faʻaalia ai o le gaioiga a le DA e le gata e fesuisuiaʻi pe mautinoa pe leai se taui (Faʻatonu Faʻatonu) poʻo le le mautinoa (Variable Ratio), ae e fesuisuiaʻi foʻi i le tele o faʻamatalaga e uiga i le tuʻuina atu o taui na faʻaalia e le CS. I le 100% tulaga, o le CS e faʻaalia ai le faʻamoemoeina o le taui ma faʻamaonia lelei lona tuʻuina atu. I le 25 ma le 75% tulaga, o le CS e faʻaalia le faʻamoemoe ma vaʻai le tuʻuina atu o taui faʻatolu mai le fa taimi. I le tulaga 50% o le CS e faʻaalia ai le faʻamoemoe ae leai se faʻamatalaga e uiga i le tuʻuina atu o taui i tua atu o le avanoa. Faʻavae i luga oa latou sailiga, Fiorillo et al. na faaiuina: "O lenei le mautinoa-faʻateleina le faateleina o le dopamine e mafai ona saofagā i le tauia o meatotino o taaloga faitupe" (itulau 1901).
The effects of 50% variable reward in a single session should not change over the course of multiple sessions because the likelihood of reward remains entirely unpredictable on every trial. Thus, when considering the conditions that would maximize chronic activation of DA neurons over repeated episodes of gambling the 50% schedule should engender the most enduring as well as the most robust effect. This is noteworthy given that the long run rate of reward (payoff > 0) observed over thousands of spins on a commercial slot machine was 45.8% (Tremblay et al., 2011). O le mea lea, 50% taui fesuia'i e foliga mai e atagia sa'o ai le fa'asologa o totogi o lo'o fa'atinoina e masini tau tupe.
O le suʻesuʻega o loʻo i ai nei na faʻaaogaina ai faʻatulagaga tutusa e pei o Fiorillo et al. i se fa'alavelave fa'afuase'i, va-vaega 'mamanu ma isumu. O manu na faia ~ 3 vaiaso o faʻasalalauga i aso taʻitasi, lea na faʻapipiʻiina ai se CS (malamalama) ma se US (laʻititi laʻititi o le sucrose). Ina ua mae'a le vaega o a'oa'oga, sa malolo manu a'o le'i faia le su'esu'ega o le fa'alogoina fa'asinoina e le locomotor tali i le amphetamine. Faʻavae i luga o tusitusiga, na valoia ai o isumu e faʻaalia i faʻasologa o taui eseese o le a le eseese i a latou amioga locomotor e leai ni fualaau faʻasaina ae o le a faʻaalia le tele o tulaga eseʻese o locomotion pe a uma le amphetamine, faatasi ai ma le 50% vaega faʻaalia se tali sili atu locomotor i le vailaʻau faʻatatau i. o isi vaega i le faagasologa o tui, o se mamanu e faʻamoemoeina pe a fai o le 50% o manu na faʻaalia muamua i tui faaopoopo o le amphetamine lava ia (ie, cross-sensitization).
Faʻamatalaga 1
Mea ma Metotia
Mataupu
E fa vaega (n = 8 / vaega) o tagata matutua (300-350 g) male Sprague-Dawley rats (Charles River, St. Constant, Quebec, Kanata) sa faʻapipiʻiina taʻitoʻatasi i totonu o pusa polycarbonate manino (20 × 43 × 22 cm) i lalo ole 12 faʻasolosolo: 12 taamilosaga malamalama-pogisa. Sa latou mauaina ad libitum access to food and water, and daily handling by an experimenter for 2 weeks prior to the study. Each group was conditioned under one of four variable reward schedules: 0, 25, 50, or 100%. The 75% group was omitted in this initial study, as Fiorillo et al. (2003) found equivalent post-CS DA release under 25 and 75% reward schedules, such that both conditions led to greater DA release than did the 100% CS-US condition, but less than the 50% condition.
Meafaigaluega
Avanoa i sucrose presentations ma le CS na tuʻuina atu taʻitasi i pusa faʻapipiʻi faʻaogaina (33 × 31 × 29 cm). O pusa taʻitasi sa faʻapipiʻiina ma se mekasini faʻamalosi, o loʻo i luga o le puipui pito i luma. O se moli i le pito i luga o le mekasini sa avea ma CS. E mafai ona sii a'e i luga o le fola o le mekasini se masini vai e pulea le solenoid. O mea na tutupu i totonu o le atigipusa na pulea e Med Associates meafaigaluega ma polokalama, faʻaaogaina se polokalame i totonu o le fale na tusia i le MED-PC. O suʻega Locomotor sa faia taʻitoʻatasi i totonu o fale Plexiglas (27 × 48 × 20 cm). O fale ta'itasi sa fa'apipi'iina i se faiga mata'ituina e aofia ai sela e ono o ata-beam e iloa ai le fegasoloa'i fa'alava.
taualumaga
aʻoga. O le suʻesuʻega na faia i le tausisia o taʻiala faʻapitoa na faʻataʻatia e le Canadian Council on Animal Care. O isumu na fa'agata i mea'ai i le 90% o le mamafa o latou tino mo le umi o le su'esu'ega ma fa'afale ta'ito'atasi. Na maua e isumu taʻitasi aso 15 o aʻoaʻoga taui sucrose (10% vai vai i le 0.06 ml i le taui): 5 aso sosoo × 3 vaiaso, faʻatasi ai ma faaiuga o vaiaso. Sa tausia manu i luga o taumafa masani a'o le'i mae'a le vaega o toleniga; na fa'atapula'aina le fa'aalia o le sucrose i le sefululima ~ 40-min a'oga. O sauniga taʻitasi i aso taʻitasi e aofia ai le 15 faʻamalositino faʻalauiloa (se moli; CS), taʻitasi taʻitasi e vavaeeseina e se vaeluaga o le 120 s. O le moli sa tu i le pito i luga o le laupepa o le mekasini, ma tumau pea mo le 25 s, ma le sucrose na avanoa i le 5 s mulimuli. I le tulaga o le vaega 0, o le sucrose dipper e siitia i le 140 s (mo le 5 s) ae e leʻi faʻamalamalamaina le moli faʻaosofia. O le mea lea na fa'atusalia ai le va i le va o fa'aaliga a le dipper i le vaega 0 ma isi vaega (120 + 25 s). O togafitiga taʻitasi e umi ~ 40 min. I le averesi, o le vaega 25 na mauaina le sucrose e tasi mo fa'aaliga uma e fa CS; O le vaega 50 na mauaina le sucrose e tasi mo fa'aaliga uma e lua CS, ma le vaega 100 na mauaina le sucrose pe a uma fa'aaliga CS uma.
tofotofoga. Lua vaiaso talu ona maeʻa le sucrose avanoa mulimuli (poʻo le "conditioning"), na iloiloina le tali a le locomotor i le d-amphetamine (AMPH; ip). Na tu'uina atu i iole ni vasega 2-h e tolu e masani ai i pusa locomotor, sosoo ai ma le ono su'ega AMPH. Ole su'ega AMPH na tupu ile 1-wk vaeluaga. I aso o suʻega, na tuʻuina atu i ai le 30 min e masani ai i pusa ona maua ai lea o se tasi 0.5 mg / kg dose o le AMPH sosoo ai, i vasega eseese o vaiaso, e lima 1.0 mg / kg doses (tasi le dose i le aso) i aso suʻega 1 i le 5. . Post-AMPH locomotion na iloiloina mo 90 min i vasega taʻitasi.
Fa'amatalaga au'ili'ili
Sa faia su'esu'ega fa'amaumauga ma le SPSS (f. 16 ma le v. 21; SPSS Inc., Chicago IL). Ole tali vave ole amio ile CS na su'esu'eina ile tu'i o le isu ile avanoa na tu'u ai le sucrose. Ole fua ole numera ole isu ile taimi ole taimi lea (5 s ile faamasinoga) ona faʻatusatusa lea ile numera ole numera ole isu mo le umi lava e tasi (5 s) averesi ile taimi na toesea ai le CS. Vaega × Sauniga ANOVA o isu-tu'i isu ma CS o lo'o iai ma toesea na su'esu'eina le mauaina o le fa'aituau e tali atu i le fa'ailoga ma le fa'aituau tali tu'i isu i lalo o fa'asologa eseese i le faagasologa o le 15 a'oga sucrose.
O aʻafiaga o togafitiga i luga o le locomotor tali na suʻesuʻeina i le Vaega × Session ANOVAs mo le faʻaogaina o fualaau faʻasaina (tolu vasega), faʻamuamua 0.5 mg / kg AMPH luʻitau (tasi vasega), ma i le taimi o le lima-vaega 1 mg / kg AMPH faiga fa'alogona, pe'ā fa'amoemoe e 'ese'ese vaega i le tali atu i fa'auiga faifaipea o le AMPH. Vaega × Session ANOVAs na suʻesuʻeina foi tali o locomotor e leai ni vailaʻau i le taimi o le 30-min aʻo leʻi tuiina le faʻataʻitaʻiga vaega mai suʻega AMPH taʻitasi. O fa'atusatusaga fuafuaina na su'esu'eina le ese'esega o le fa'atinoina o galuega mo le vaega 50 vs. vaega 0 (leai se fa'atonuga fa'amoemoe) ma le vaega 100 (leai se fa'atonuga fa'aletonu), e ala i le t-tesega (Howell, 1992), using the MS error and df error terms for the relevant effect (i.e., group or group × session interaction) from the ANOVA (Winer, 1971). O su'esu'ega a le Polynomial na fa'ata'ita'iina ai le talaaga o suiga i le gasologa o vasega.
Ina ia iloa pe o tali atu i le i ai ma le toesea o le CS i le taimi o le 15 sucrose training sessions na saofagā i le fesuiaiga o le locomotor tali i le AMPH, poʻo le faʻatalanoaina o le eseesega o vaega i le AMPH tali, suʻesuʻega tulitatao o covariance (ANCOVAs) na faia i le AMPH. fa'amaumauga o locomotor, e aofia ai le aofa'i o tui isu (se aofa'iga mo le 15 vasega) pe a to'esea le CS o le covariate. O se aafiaga taua o le covariate o le a faailoa mai ai o tali e leai se fualaau faasaina e faʻafetaui (aʻafia ai le malosi o) aʻafiaga o le vaega poʻo le sauniga. O le fa'aitiitia o le taua o a'afiaga o kulupu po'o le sauniga i le i ai o se fa'atasiga taua e fa'ailoa mai ai o tali fa'alatalata e fa'atalanoaina (tuuina mo) a'afiaga o kulupu po'o le sauniga. O le fa'aitiitia o le taua o le vaega po'o le a'afiaga o le sauniga i le leai o se fa'alavelave taua tele o le a atagia mai ai le leiloa o le malosi fa'afuainumera ona o le toe fa'avasegaina o le df mai le taimi sese i le covariate, ma e le mafai ona fa'atatau i le fa'amatalaga o le aafiaga o vaega po o sauniga.
i'uga
Tu'i isu ile taimi ole sucrose conditioning
CS o lo'o iai. Ata 1A o loʻo faʻaalia ai le uiga o le isu o le isu mo vaega 25, 50, ma le 100 aʻo iai le CS i le 15 sucrose conditioning sessions (e leʻi faʻailogaina le isu mo le kulupu 0, e leai se CS). O le 3 Group × 15 Session ANOVA na maua mai ai aafiaga autu taua o le Vaega, F(2, 21) = 5.63, p = 0.011, ma le Sauniga, F(14, 294) = 14.00, p <0.001, fa'atasi ai ma se feso'ota'iga tele a le Vaega × Session, F(28, 294) = 2.93, p <0.001. Ata 1A O lo'o fa'ailoa mai o le a'afiaga autu o le Sauniga na atagia mai ai le fa'atupula'ia o le isu i le va o vasega i vaega uma e tolu, ma o le a'afiaga autu o le Vaega e atagia mai ai le maualuga maualuga o sikoa i le vaega 100 vs. vaega 25 ma togi vaeluaga i le vaega 50. O se Vaega taua × Session. fegalegaleaiga mo le tulaga kupita, F(2, 21) = 4.42, p = 0.030, ua faʻaalia ai le vave oso aʻe, faʻafefe, ma le faʻafefe o le isu i luga o vasega i le vaega 100, e faʻatatau i se faʻaopoopoga laina i luga o vasega i le vaega 50, ma le siʻitia laina papaʻu i luga o vasega i le vaega 25.
Figure 1. Mean (SE) approach responses (nose pokes) on 15 sucrose training sessions in groups of Sprague Dawley rats (n = 8 / vaega) faʻaalia i le sucrose taui (10% solution) tuʻuina atu i lalo ole 0, 25, 50, poʻo le 100% faʻasologa fesuiaiga. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. (A) Scores when CS was present (5 s × 15 trials). (B) Scores when CS was absent (average for 5 × 15 s while light was off).
CS toesea. Ata 1B o lo'o fa'aalia ai le fa'aoso o le isu mo vaega uma e fa mo se taimi tutusa (5 s × 15 fa'ata'ita'iga) fa'atatau ile taimi na toesea ai le CS. O le 4 Group × 15 Session ANOVA na maua mai ai aafiaga taua o le Vaega, F(3, 28) = 7.06, p = 0.001, ma le Sauniga F(14, 392) = 2.84, p <0.001, fa'atasi ai ma se feso'ota'iga tele a le Vaega × Session, F(42, 392) = 3.93, p <0.001. Ose vaega tele × Feso'ota'iga mo le fa'asologa fa'afa'afa, F(3, 28) = 3.91, p = 0.019, faatasi ai ma le leai o se fegalegaleaiga mo le tulaga kupita, F(3, 28) <0.93, p > 0.44, ua atagia mai ai le fa'ailoga "Fua'i-U" o tui isu i vasega i le vaega 0, e fa'asaga i se fa'amatalaga mautu i luga o vasega i isi vaega.
Mauaina i potu locomotor
O le 4 Group × 3 Session ANOVA na maua ai se aafiaga autu o le Sauniga, F(2, 56) = 5.67, p = 0.006, ma e leai se isi aafiaga taua, F(3, 28) <1.60, p > 0.21. Mean (SE) fa'amavae i le 2 h i totonu o pusa locomotor e 1681 (123) i le vasega 1, 1525 (140) i le vasega 2, ma le 1269 (96) i le vasega 3. O fa'atusatusaga fuafuaina e leai se eseesega tele i le va o le vaega 50 ma le vaega. 0 poʻo le vaega 100 i le sauniga masani muamua poʻo le mulimuli, t(84) <1.69, p > 0.05. O le mea lea, i le leai o le AMPH, o le faʻaalia faifaipea i pusa suʻega na fesoʻotaʻi ma le faʻaitiitia faifaipea o le gaioiga faʻafuaseʻi i vaega e fa (ie, Session effect), ma e leai se tali eseʻese e avea o se galuega o le sucrose aʻoaʻoga faʻatulagaina (leai se fegalegaleaiga) .
Su'ega vasega
A'afiaga o le mua'i lagona 0.5 mg/kg AMPH lu'i.
A'o le'i tui tui. O le 4 Group one-way ANOVA o locomotor tali i le taimi o le 30-min pre-injection habituation vaega e leai ni aafiaga taua, F(3, 28) <1.05, p > 0.38. O faʻatusatusaga fuafuaina e leai se eseesega tele i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100, t(32) <0.87, p > 0.40. O le mea lea, o eseesega faʻavae i le locomotion aʻo leʻi tuiina e leʻi faʻamatalaina le eseesega o vaega ile tali ole locomotor ile AMPH. O lona uiga (SE) fa'alava mo le fa'ata'ita'iga e 559 (77).
O locomotion pe a mae'a tui vs. fa'au'uga fa'ato'aga e leai se vaila'au. O le 4 Group × 2 Session ANOVA faʻatusatusa tali a locomotor vaega i le faʻasalaga mulimuli, ma i le taimi lava na maeʻa ai le 0.5 mg / kg AMPH luʻitau muamua. O sikoa mo le faʻasalalauga masani (120 min) na faʻatulagaina e fetaui ma le umi o le suʻega a le AMPH (90 min) (mataʻu masani × 90/120). O le au'ili'iliga na maua ai se aafiaga taua tele o le Sauniga, F(1, 28) = 34.16, p <0.001, ma e leai se isi aafiaga taua, F(3, 28) <2.26, p > 0.10. O le a'afiaga o le Sauniga na atagia ai le fa'atuputeleina o le ave (SE) fa'amavae i le tali atu i le fua, mai le 952 (72) i le 1859 (151). O faʻatusatusaga fuafuaina e leai se eseesega tele i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100 i le tali atu i le fua, t(56) <1.72, p > 0.10. Ae ui i lea, o le faʻasologa o le faʻasologa o togi faʻamau (M; SE) e fetaui lelei ma le manatu: vaega 50 (2205; 264) > vaega 0 (2025; 203) > vaega 100 (1909; 407) > vaega 25 (1296; 299) .
Aafiaga ole 1 mg/kg AMPH.
A'o le'i tui tui. O le 4 Group × 5 Session ANOVA o le locomotor tali i le taimi o le 30-min pre-injection habituation phase i luga ole 1 mg / kg AMPH suʻega faʻataʻitaʻiga na maua ai se aafiaga autu o le Sauniga, F(4, 112) = 43.64, p <0.0001, ma e leai se isi aafiaga taua, F(3, 28) <0.97, p > 0.42. O faʻatusatusaga fuafuaina e leai se eseesega tele i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100 i le suʻega muamua poʻo le suʻega mulimuli, t(140) <0.84, p > 0.30. O le mea lea, o eseesega faʻavae i le locomotion e leʻi faʻamatalaina le eseesega o vaega i le tali a le locomotor i le AMPH. Mean (SE) fa'ailoga fa'alava mo le fa'agasolo a'o le'i faia le fa'aoga i vasega 1-5 e: 454 (30), 809 (53), 760 (36), 505 (35), 756 (39).
Fa'ato'a tui. Ata 2 e fa'aalia ai a'afiaga o tui e lima ole 1 mg/kg AMPH (tasi i le vaiaso) i sikoa o le locomotor i vaega e fa. O le 4 Group × 5 Session ANOVA na maua ai se aafiaga autu o le Sauniga, F(4, 112) = 8.21, p <0.001, ose a'afiaga fa'apitoa ole Vaega, F(2, 45) = 3.28, p = 0.085, ma e leai ni fegalegaleaiga taua, F(12, 122) <0.77, p > 0.68.
Figure 2. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) to 1 mg/kg d-amphetamine (i.p.) on 5 weekly sessions in groups of Sprague Dawley rats (n = 8/group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. *p < 0.05 for mean difference between group 50 and group 0 as well as group 100, based on planned comparisons.
O faʻatusatusaga fuafuaina na faʻaalia ai o le vaega 50 togi e matua ese lava mai le vaega 0, t(14) = 2.19, p = 0.037, ma le vaega 100, t(14) = 2.36, p = 0.025 [ma e ese mamao mai le vaega 25, t(14) = 2.03, p = 0.051]. O le mea lea, i le vaega 50, o le tali a le locomotor i le 1 mg / kg AMPH faʻalagolago na sili atu nai lo isi vaega e tolu i vaega uma o suʻega e lima. Ole su'esu'ega ole polynomial na maua ai se fa'asologa fa'afa'afa taua ile vasega, F(1, 28) = 32.47, p <0.0001, ma e leai se isi faiga taua, F(1, 28) <1.78, p > 0.19. Ata 2 o lo'o fa'aalia ai o lenei fa'ai'uga na atagia mai ai le fa'ata'ita'iga o le "U fa'aliliuina" i vasega.
Puleaina mo le fesuisuiai o le tali atu o tui isu i le taimi o aoaoga sucrose
O le tulitatao ANCOVA o locomotor tali i le 1 mg / kg AMPH, faʻatasi ai ma le isu o loʻo i ai (CS o loʻo i ai) e pei o le covariate, i vaega e tolu na mauaina le CS, na maua ai se aʻafiaga autu o le Vaega, F(2, 20) = 3.07, p = 0.069, ma e leai ni a'afiaga taua e feso'ota'i fa'atasi, F(4, 80) <0.05, p > 0.85. O le mea lea, o le faʻaogaina o le tali atu i le taimi o aʻoaʻoga e leʻi faʻamatalaina ai se eseesega tele i le tali o le locomotor i le 1 mg / kg AMPH i vaega 25, 50, poʻo le 100.
O le tulitatao ANCOVA o tali o locomotor i le 1 mg / kg AMPH, faʻatasi ai ma le isu o le isu (CS toesea) e pei o se covariate, na maua ai se aafiaga taua o le covariate, F(1, 27) = 6.17, p = 0.020, o se aafiaga taua tele o le Vaega, F(3, 27) = 4.13, p = 0.016, se Sauniga fa'aitiitiga × Feso'ota'iga fa'atasi, p = 0.080, ma e leai se isi aafiaga taua, F(4, 108) <1.48, p > 0.21. O le mea lea, o le tali atu i le taimi o aʻoaʻoga e le faʻaalia (le faʻaituau) na faʻamatalaina ai le tele o suiga i le tali a le locomotor i le 1 mg / kg AMPH. Ae ui i lea, o lenei fesuiaiga e leʻi faʻafefeteina ma le faʻaogaina o vaega, ona o le aofia ai o le covariate i le auʻiliʻiliga na faʻateleina nai lo le faʻaitiitia o le taua o le aʻafiaga o vaega.
Talanoaga
O fa'amatalaga tu'i isu a'o iai le CS o lo'o fa'aalia ai na maua e kulupu le feso'ota'iga i le va o le CS ma le tu'uina atu o le sucrose e pei ona atagia mai i le fa'ateleina o tali fa'asino i taimi o toleniga. O le talaaga o le tali atu i vasega aʻo iai le CS na fautua mai ai o le 100 ma le 50% CS-US faʻatulagaina na tutusa lelei i le faʻaalia o le auala, ae o le 25% faʻasologa na faʻaalia ai se faʻaopoopoga sili atu i le faʻaogaina o auala. O faʻamaumauga o le isu aʻo le i ai le CS o loʻo fautua mai ai o vaega na mauaina soʻo se tolu CS-sucrose faʻasologa o aʻoaʻoga (vaega 25, 50, 100) vave ona aʻoaʻoina e faʻaitiitia o latou isu pe a leai se CS, ae o manu i le vaega 0 , lea e leai se CS, naʻo le aʻoaʻoina e faʻaitiitia a latou amio faʻalatalata i se tikeri faʻatapulaʻa pe a maeʻa aʻoaʻoga tele.
O faʻamaumauga masani e faʻaalia ai e leʻi eseese vaega aʻo leʻi oʻo i le AMPH ma o le faʻaalia faifaipea i pusa suʻega na fesoʻotaʻi ma le faʻaitiitia o le tali atu o locomotor e leai ni fualaau. O le mea lea, o eseesega i le va o kulupu ma le faʻateleina o le tali atu i luga o faʻasologa faifaipea o le AMPH e le mafai ona faʻatatau i eseesega o loʻo i ai muamua i le locomotor amioga.
I'uga o le lu'itau a'o le'i fa'alogoina ma le 0.5 mg/kg AMPH na fa'amaonia ai o le vaila'au na fa'ateleina le gaioiga o le locomotor e fa'atatau i le aso mulimuli e leai ni fualaau fa'asaina. E tusa ai ma le manatu, o le vaega 50 e maualuga atu nai lo vaega 0 poʻo le 100 (faʻapea foʻi ma le kulupu 25) e tusa ai ma le uiga o le tali atu i le fua, e ui o le eseesega o eseesega i le va o vaega e le taua.
Mo faʻasalalauga faʻapitoa, o faʻatusatusaga fuafuaina i le va o vaega na faʻaalia ai o le faʻaalia muamua i le 50% conditioned sucrose taui na taʻitaʻia ai le faʻatupulaia tele o le tali atu i le 1.0 mg / kg dose o le amphetamine e faʻatatau i isi faʻatulagaga e tolu. O lenei a'afiaga na fa'aalia mai le tui muamua ma e le'i suia tele i luga o tui fa'aauau. O le au'ili'iliga masani na fa'aalia ai se tali biphasic (mo le fa'ata'ita'iga atoa) i toso fa'asolosolo o le AMPH, fa'atuputeleina e o'o i le tui lona tolu ma fa'aitiitia mulimuli ane. O taunuʻuga o le tulitatao ANCOVA faʻatasi ai ma le isu-pokes (CS toesea) e pei o le covariate na faʻamaonia ai o eseesega i tali o locomotor vaega e fa i le 1 mg / kg AMPH e leʻi faʻatalanoaina e ala i le tali atu i le taimi o aʻoaʻoga sucrose.
O le a'afiaga o fa'alapotopotoga i taimi o fa'asalalauga fa'apitoa e fetaui lelei ma la tatou fa'aaupuga. Ole a'afiaga ole bi-phasic e le o ogatasi ma le fa'amoemoega fa'atuputeleina fa'atuputeleina i tali locomotor fa'atasi ai ma fa'asologa o AMPH. E ono feso'ota'i lenei mea ma le va o le fa'ataga. Ina ia foia lenei mataupu, e tatau ona faʻaaogaina se faʻataʻitaʻiga (suʻi faʻasologa o aso taʻitasi) e faʻaalia e faʻaosofia ai le faʻateleina o le tali atu o locomotor i 1.0 mg / kg doses o le AMPH (ie, faʻalogoina o amioga) e tatau ona faʻaaogaina. O le aʻafiaga o se faʻatonuga faʻapitoa a le AMPH i luga o le tali mulimuli ane i se luʻitau lona lua 0.5 mg / kg o le a lagolagoina atili ai le lautele o lenei aafiaga. O le fa'aofiina o se lu'itau masima a'o le'i o'o i le AMPH o le a fuafua ai le matafaioi o le fa'amoemoe po'o le tui-fa'ata'ita'iga (fa'ata'ita'iga, fa'alavelave) a'afiaga i le tali atu o locomotor i le AMPH. O le faʻaofiina o le 75% conditioned sucrose group o le a fesoasoani e faʻamalamalamaina le matafaioi o le le mautonu o le taui ma le le mautonu o taui i luga o le mamanu o tali mo vaega 50 ma le vaega 25. E le gata i lea, ia faʻatagaina le iloiloga (e le ANCOVA) o le sao o fualaau faasaina. e fa'asino i tali i le gaioiina i lalo o le AMPH (fa'aaogaina o tui isu ma le CS o lo'o i ai e pei o le covariate), sa fa'ailogaina fo'i isu mo le vaega 0 i le va o le va o le CS i isi vaega e fa (fa'atusa, ina ia oso le isu mai vaega uma e lima. vaega-e aofia ai le vaega 0 e leai se CS-e mafai ona aofia i le auiliiliga o le covariance ma CS o loʻo i ai o le covariate). O nei faʻaleleia na tuʻufaʻatasia i le faʻataʻitaʻiga 2.
Faʻamatalaga 2
Mea ma Metotia
The methodology of experiment 2 was similar to that of experiment 1 but revised to better approximate a regimen found to reliably induce AMPH sensitization (Fletcher et al., 2005). O suiga e pei ona taua i lalo: (a) O le 75% CS-sucrose group (n = 8) na aofia ai; (b) I le taimi o aʻoaʻoga sucrose, na maua e iole (sei vagana ai le vaega 0) 20 CS (malamalama) faʻaaliga (e ese mai le 15 i le faʻataʻitaʻiga 1); (c) O fa'aaliga CS na tu'u'ese'ese ta'itasi ile va ole va ole fa'amasinoga ole 90 s; laina: 30-180 s (vs. 120 s i le faʻataʻitaʻiga 1), lea e faʻafefe ai le faʻateleina o faʻataʻitaʻiga aʻoaʻoga e faʻatusatusa ai le umi o aʻoaʻoga taʻitasi i le faʻataʻitaʻiga 1; (d) o le umi o sauniga masani e tolu na faaitiitia mai le 120 i le 90 minute ina ia fetaui ma le umi o suʻega; (e) O se saline (ip, 1 ml / kg) luʻitau (90 min) na faʻaopoopoina (aso 8 aʻoaʻoga post-sucrose), e iloilo ai aʻafiaga o locomotor o tui. taʻitasi (fa'ata'ita'iga, fa'amoemoe, fa'alavelave); (f) O le 1 mg/kg sensitization sessions sa faia i isi aso o le vaiaso (aso i tua o aʻoaʻoga 12-21) nai lo taimi taʻitasi vaiaso e pei o le suʻega 1; (g) Faʻatasi ai ma le faʻataʻitaʻiga 0.5 mg / kg AMPH luʻitau (aso-aʻoaʻoga aso 9) na faʻaopoopoina se faʻataʻitaʻiga lona lua 0.5 mg / kg AMPH luʻitau (post-sucrose training day 28), e suʻe ai le lautele o le aafiaga lagona i luga ole tui; (h) tui isu a'o iai CS sa fa'ailoga mo vaega uma (e aofia ai le vaega 0); (i) tui o le isu a'o toesea CS na fa'amauina fa'apitoa mai le va o le 5-s a'o le'i amataina le CS e fa'asino le tali vave.
i'uga
Tu'i isu ile taimi ole sucrose conditioning
A 5 Vaega × 15 Sauniga × 2 Vaega (CS o loʻo i ai, CS toesea) ANOVA o tui isu na maua ai aʻafiaga autu taua ole Vaega, F(4, 19) = 2.89, p = 0.050, Sauniga F(14, 266) = 2.28, p = 0.006, ma le Vaega, F(1, 19) = 14.72, p = 0.001, faʻapea foʻi ma se fesoʻotaʻiga taua e tolu auala, F(56, 266) = 1.38, p = 0.050. Panela (A, B) o Ata 3 Fuafua fa'ailoga tu'i isu a vaega mo le CS o lo'o iai ma le CS toesea, fa'asologa. Fa'atusatusaga o paneli e lua e fa'aalia ai o le a'afiaga autu o le Vaega na atagia mai ai le tele o tali tu'i isu pe a iai le CS vs. O le mea lea, o tali fa'ailoa na tupu tele i le tele o taimi nai lo tali vave e le'i fa'ailoaina. O a'afiaga autu o le Vaega ma le Sauniga e le'i faigofie ona fa'amatalaina ona o le fa'atonuga maualuga. O le i'uga mulimuli lea na atagia mai ai le fefiloi o togi mo vaega e lima i se tulaga maualalo mautu i vasega uma ina ua toesea le CS (Ata 3B), faatasi ai ma se eseesega o togi i le maualuga (vaega 75, vaega 100), vaeluaga (vaega 50), ma le maualalo (vaega 0, vaega 25) tulaga o tui isu e tali atu i vasega pe a iai le CS (Ata 3A). Mai le fa'atonuga pito i lalo polynomial faiga (linear, quadratic, cubic) na'o le tolu-auala fegalegaleaiga mo le laina laina na latalata i le taua, F(4, 19) = 2.32, p = 0.094, e atagia ai le faʻateleina o le faʻateleina o le isu i luga o sauniga i le vaega 75 ma sili atu le vave faʻamautuina i le maualuga, vaeluaga, ma le maualalo o le tali atu i isi vaega pe a iai le CS.
Figure 3. Mean (SE) approach responses (nose pokes) on 15 sucrose training sessions in groups of Sprague Dawley rats (n = 8 / vaega) faʻaalia i le sucrose taui (10% solution) tuʻuina atu i lalo ole 0, 25, 50, 75, poʻo le 100% faʻasologa o suiga. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. (A) Scores when CS was present (5 s × 20 trials). (B) Scores when CS was absent (average for 5 × 20 s while light was off).
Mauaina i pusa locomotor
O le 5 Vaega × 3 Session ANOVA o tali locomotor e leai ni fualaau faasaina na maua ai se aafiaga taua tele o le Sauniga, F(2, 70) = 60.01, p <0.0001, ma e leai se isi aafiaga taua, F(4, 35) <0.70, p > 0.60. Fuafuaga fa'atusatusaga o le vaega 50 ma le vaega 0 ma le vaega 100 i le taimi muamua ma le fa'ai'uga fa'atasiga e leai ni a'afiaga taua, t's <0.84, p > 0.40. Ole mea lea, ole tali ole locomotor e leai ni vaila'au i vaega autu e le'i ese a'o le'i faia su'ega. O le aofa'i (SE) numera o fa'alava i le 90 min e 2162 (118) ile vasega 1, 1470 (116) ile vasega 2, ma le 1250 (98) ile vasega 3.
Su'ega vasega
Saline. O le 5 Vaega × 2 Sauniga ANOVA fa'atusatusa le tali a le locomotor i le sauniga fa'ai'u ma le lu'itau saline. O le ANOVA na maua ai se aafiaga autu o le Sauniga, F(1, 35) = 62.46, p <0.0001, ma e leai se isi aafiaga taua, F(4, 35) <0.65, p > 0.64. Ata 4 taupulepule le vaega o lona uiga ma faʻaalia ai o le aʻafiaga o le Sauniga na atagia ai le faʻaitiitia atoa o le tali mai o le locomotor mai le taimi mulimuli e leai se fualaau faʻasaina i le saline, lea e leʻi eseese i vaega. O le mea lea, o le faʻaitiitia o le tali atu o locomotor na vaʻaia i luga o faʻasalalauga e tolu na faʻaauau pea i luga o le faʻaalia o fualaau faʻasaina i pusa suʻega.
Figure 4. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) on the last of 3 drug-free habituation sessions and on a subsequent session after saline injection (i.p., 1 ml/kg) in groups of Sprague Dawley rats (n = 8/group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, 75, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli.
Aafiaga ole 0.5 mg/kg AMPH.
A'o le'i tui tui. A 5 Vaega × 2 Session ANOVA o locomotion muai tui (30-min) i luga o le muamua ma le post-sensitization 0.5 mg / kg AMPH suʻega aso na maua ai se aafiaga taua tele o le Sauniga, F(1, 35) = 13.39, p = 0.001, ma e leai se isi aafiaga taua, F(4, 35) <1.79, p > 0.15. O faʻatusatusaga fuafuaina e leai se eseesega tele i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100 i le vasega muamua, t(70) <1.00, p > 0.30. Ae ui i lea, i luga o le vaega lona lua (post-sensitization) vaega 50 (1203; 121) na faʻaalia ai le sili atu o le vaʻa o le faʻamaʻi (M; SE) nai lo le vaega 100 (756; 103), t(70) = 5.11, p <0.001, ae le'i ese mai le vaega 0 (1126; 211), t(7) <0.88, p > 0.40. O le mea lea, o eseesega faʻavae i le locomotion e leʻi faʻamatalaina mo eseesega vaega i le locomotor tali i le 0.5 mg / kg muamua dose o le AMPH ae atonu na saofagā i le eseesega i le va o le vaega 50 ma le vaega 100 i le locomotor tali i le lona lua 0.5 mg / kg dose o le AMPH. . Mean (SE) pa'u mo le vaega a'o le'i tui i le 0.5 mg/kg su'ega AMPH muamua ma lona lua e 757 (41) ma le 974 (59).
Fa'ato'a tui. O le 5 Group × 2 Session ANOVA o le locomotor tali i le 0.5 mg / kg AMPH aʻo leʻi maeʻa le 5-dose sensitizing regimen na maua ai se aʻafiaga autu o le Sauniga, F(1, 35) = 76.05, p <0.0001, ma e leai se isi aafiaga taua, F(4, 35) <1.10, p > 0.37. Ata 5 o lo'o fa'aalia ai togi fa'atatau mo vaega ta'itasi ma vasega.
Figure 5. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) to 0.5 mg/kg d-amphetamine on separate sessions before and after a 5-session sensitizing regimen of d-amphetamine (1.0 mg/kg; i.p. per session) in groups of Sprague Dawley rats (n = 8/group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, 75, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. *p < 0.05 for mean difference between group 50 and group 0 as well as group 100, based on planned comparisons.
O le fuainumera o loʻo faʻaalia ai o le aʻafiaga o le Sauniga na aʻafia ai se faʻaopoopoga tele i le aofaʻi atoa (SE) faʻamavae i le 90 min mai le 0.5 mg / kg dose 1, 3674 (216) i le 0.5 mg / kg dose 2, 6123 (275). O le leai o se fegalegaleai poʻo le aʻafiaga o kulupu na fautua mai ai o le faʻalogo i le AMPH e leʻi fesuisuiaʻi faʻalagolago i vaega. E ui i le leai o ni a'afiaga fa'apitoa e feso'ota'i i vaega i le ANOVA, o le su'esu'ega o le fuainumera e fa'aalia ai o le vaega 50 na fa'aalia le tali sili i le muamua ma le lona lua 0.5 mg/kg doses. Fuafuaga faʻatusatusaga o le tali atu i le 0.5 mg / kg fua muamua na faʻaalia ai e leai se eseesega tele i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100, t's(35) <0.48, p > 0.50. Ae ui i lea, i le tali atu i le lona lua (post-sensitization) 0.5 mg / kg dose, o le vaega 50 na faʻaalia le sili atu o locomotion nai lo le vaega 0, t(35) = 2.00, p <0.05, faʻapea foʻi ma le vaega 100, t(35) = 3.29, p <0.01.
E tusa ai ma le eseesega tele o vaega i le locomotion muamua tui i luga o le 0.5 mg / kg AMPH sauniga lona lua na lipotia i luga, o se tulitatao 5 Group × 2 Session ANCOVA o le locomotor tali i le 0.5 mg / kg AMPH sa faia, pulea mo le muai- tui locomotion i le vasega lona lua. O lenei auiliiliga na maua ai se aafiaga taua o le covariate, F(1, 34) = 8.65, p = 0.006, o se aafiaga autu o le Sauniga F(1, 34) = 10.83, p = 0.002, ma e leai se isi aafiaga taua, F(4, 34) <0.85, p > 0.50. O le mea taua, o faʻatusatusaga fuafuaina e faʻavae i luga o le MS error ma le df error mai le ANCOVA na faʻamaonia ai o le tali o le locomotor i le 0.5 mg / kg lona lua o le AMPH na tumau pea le sili atu i le vaega 50 nai lo le vaega 100, t(34) = 3.09, p <0.01, ma le vaega 0, t(34) = 1.88, p <0.05 (tasi le si'usi'u), ina ua pulea le suiga muamua o tui mai le vasega 2. O le mea lea, o le vaega 50 na faʻaalia le sili atu o le tali atu o locomotor i le 0.5 mg / kg AMPH nai lo le vaega 100 poʻo le vaega 0, ma o nei eseesega vaega e leʻi faʻatalanoaina e ala i le faʻaogaina muamua o le tui i aso o suʻega.
Aafiaga ole 1.0 mg/kg AMPH.
A'o le'i tui tui. O le 5 Group × 5 Session ANOVA o le 30-min pre-injection scores mo le 1 mg/kg AMPH sensitization sessions na maua ai se aafiaga autu o le Sauniga, F(4, 140) = 16.70, p <0.0001, ma e leai se isi aafiaga taua, F(4, 35) <0.94, p > 0.45. O faʻatusatusaga fuafuaina e leai se eseesega tele i le locomotion aʻo leʻi tuiina i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100 i le vasega muamua, t(175) <1.66, p > 0.10. Ae ui i lea, i le sauniga mulimuli, o le vaega 50 (1167; 140) na faʻaalia le sili atu o le faʻamalo o ave (M; SE) nai lo le vaega 100 (1000; 99), t(175) = 2.35, p <0.05, ae le'i ese mai le vaega 0 (1085, 120), t(175) <1.16, p > 0.20. O le mea lea, o le eseesega i le muai tui locomotion na saofagā i eseesega i le va o vaega 50 ma 100 i le locomotor tali i le 1 mg / kg AMPH mulimuli. Mean (SE) fa'amavae atoa mo le fa'ata'ita'iga i le taimi a'o le'i tu'iina vaega mo Sauniga 1 e o'o i le 5 o: 810 (46), 784 (52), 760 (53), 726 (46), 1009 (51).
Fa'ato'a tui. O le 5 Group × 5 Session ANOVA o tali i le 1 mg / kg AMPH na maua ai se aafiaga taua tele o le Sauniga, F(4, 140) = 6.72, p <0.001, o se vaega fa'aituau × Fegalegaleaiga o le Sauniga, F(16, 140) = 1.57, p = 0.085, ma e leai se aafiaga autu o le Vaega, F(4, 35) <0.44, p > 0.77. O su'esu'ega a le Polynomial na fa'aalia ai se fa'asologa tele o laina, F(1, 35) = 9.19, p = 0.005, ma le tulaga kupita, F(1, 35) = 21.63, p <0.001, i luga o vasega 1 e oo i le 5. Ata 6 o lo'o fa'aalia ai le aofa'i o togi o locomotor mo vaega ta'itasi ma le vasega.
Figure 6. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) to 1 mg/kg d-amphetamine (i.p.) on 5 weekly sessions in groups of Sprague Dawley rats (n = 8/ group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, 75, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli.
O le fuainumera o loʻo faʻaalia ai o le aʻafiaga o le Sauniga na atagia mai ai se faʻaopoopoga tele i le aofaʻi atoa (SE) faʻamavae mo le faʻataʻitaʻiga atoa mai le vasega 1, 4624 (213) i le vasega 5, 5736 (272), faʻamaonia le faʻaalia o le faʻaalia i le AMPH. O le tulaga kupita o loʻo faʻaalia ai le maualuga maualuga i vasega 1, 3, ma le 5, faʻatasi ai ma le faʻaitiitia o vasega 2 ma le 4, aemaise lava mo vaega 0 ma le 50. O loʻo faʻaalia foi e le fuainumera, e ui lava i le leai o se fegalegaleaiga taua, o le vaega 25 na faʻaalia le faasolosolo malie o le tali atu o locomotor. i luga o vasega ma e matua ese lava mai isi vaega i vasega 4 ma 5 (9 ma 22% sili atu, nai lo le isi vaega maualuga). O faʻatusatusaga fuafuaina na maua ai le vaega 50 e leʻi ese tele mai vaega 0 poʻo le 100, t(175) <0.89, p > 0.40 ile su'ega muamua po'o le mulimuli ole 1 mg/kg AMPH.
Puleaina mo le fesuisuiai o le tali atu o tui isu i le taimi o aoaoga sucrose
Lua 5 Vaega × 2 Session ANCOVAs o locomotor tali i le 0.5 mg / kg AMPH aʻo leʻi faia ma pe a maeʻa le faʻaogaina o le faʻaogaina, e aofia ai le aofaʻi o le isu i le taimi o aʻoaʻoga sucrose ma le CS o loʻo i ai ma le CS o loʻo toesea o ni mea eseese, e leai ni aʻafiaga taua mo soʻo se tasi, F(1, 18) <1.03, p > 0.31. O le mea lea, o le tali atu i le taimi o aʻoaʻoga e leʻi faʻatalanoaina eseesega o vaega i le tali atu i le 0.5 mg / kg AMPH.
Lua 5 Group × 5 Session ANCOVAs o le locomotor tali i le 1 mg / kg i le taimi o faʻasalalauga faʻatasi ma le aofaʻi o le isu (CS o loʻo i ai, CS toesea) ona o faʻasalalauga eseese e leai ni aʻafiaga taua o le covariate ao iai le CS, F(4, 104) <1.04, p > 0.38, ma se aʻafiaga autu o le covariate aʻo toesea le CS, F(1, 18) = 3.32, p = 0.085.
Talanoaga
O taunuʻuga o lenei suʻesuʻega e leʻi lagolagoina i taimi uma le manatu o le vaega 50 o le a faʻaalia le maualuga o le locomotor tali i luga o vasega faʻatusatusa i isi vaega. O le 1 mg / kg AMPH faʻamaumauga na faʻamaonia ai le tulaʻi mai o le faʻalogoina ma le faʻasologa o faʻasologa o aso. O le faʻataʻitaʻiga i vaega uma na faʻaalia ai se faʻataʻitaʻiga mo le faʻaalia atili i le taimi o sauniga mulimuli i le vaega 25, e aunoa ma se faʻamaoniga faʻapitoa mo le vaega 50. I se faʻatusatusaga, o le 0.5 mg / kg fua o fua na faʻaalia ai se tulaga mo le sili atu o le lagona i le vaega 50, ae i le tutusa. taimi e faʻamaonia ai se faʻaopoopoga tele o le tali a le locomotor i vaega i le lona lua vs. le muamua 0.5 mg / kg AMPH dose. O le aoga ole tui ole saline na faʻamaonia ai ole faʻamoemoe poʻo le faʻalavelave faʻalavelave faʻalavelave e leʻi saofagā i aʻafiaga AMPH.
The nose poke data again revealed an overall increase in approach responding over the course of training sessions when the CS was present, with no corresponding increase when the CS was absent. Therefore, the animals appeared to acquire the association between the CS and the prospect of sucrose reward. Group differences in the frequency of nose pokes when the CS was present conformed roughly to the frequency of reward delivery under the respective schedules, with groups 75 and 100 displaying the most nose pokes, group 50 displaying intermediate numbers of nose pokes, and groups 0 and 25 displaying the fewest nose pokes. These results suggest that the CS came to control approach responding in a manner consistent with the overall probability of reward. Although speculative, one possible explanation for the lower nose poke rates with CS present in group 50 in experiment 2 vs. experiment 1 may be the shortening of the inter-trial interval, as longer inter-trial intervals (experiment 1) appear to encourage impulsive tendencies and this is associated with increased turnover of DA in anterior cingulate, prelimbic and infralimbic cortices (Dalley et al., 2002). O le mea lea, o le 30% faʻaitiitiga i le va o faʻataʻitaʻiga i le faʻataʻitaʻiga 2 (ma le 3) atonu na suia ai le cortical DA maualuga ma faʻateleina le filifilia (faʻataʻitaʻiga, taʻitaʻia e le fesoʻotaʻiga o le taui) vs. tali i le vaega 50 i le taimi o aʻoaʻoga faʻataʻitaʻiga i le faʻataʻitaʻiga 2 pe a faʻatusatusa i le faʻataʻitaʻiga 1.
O le leai o ni a'afiaga e feso'ota'i fa'atasi i le isu i le CS o lo'o iai i le ANCOVA o lo'o fa'aalia ai o le tali atu i le taimi o a'oa'oga sucrose e le'i fa'atalanoaina a'afiaga o fa'asologa CS-sucrose eseese i tali i le AMPH. O le aʻafiaga taua tele o le covariate mo le CS o loʻo toesea i le ANCOVA o locomotor tali i le 1 mg / kg AMPH o loʻo fautua mai ai o le uiga o le vave tali atu e aunoa ma se fualaau faasaina na faʻamatalaina ai nisi o fesuiaiga o aʻafiaga o le AMPH i le taimi o faʻasalalauga.
Faʻatasi, o faʻamaoniga o loʻo taʻu mai ai o aʻafiaga o le faʻasologa o tala faʻasolopito atonu e sili atu ona iloatino i le 0.5 AMPH nai lo le 1 mg / kg AMPH, ma o se faʻasalalauga e faʻaalia ai le lagona i le leai o se isi togafiti e ono faanenefu pe faʻateleina ai aʻafiaga o se faʻalavelave. fa'amanino-fa'alauiloaina le fa'aogaina o amioga (fa'atusa, taui fesuisuia'i tumau).
Behavioral sensitization to AMPH is a robust effect in the laboratory. However, outside the laboratory, only a minority of individuals who gamble chronically escalate to pathological levels. Although risk for sensitization is related to risk for addiction (or drug seeking), especially for psychostimulants (Vezina, 2004; Flagel et al., 2008), many factors aside from sensitization risk may predispose one to addiction (e.g., Verdejo-Garcia et al., 2008; Conversano et al., 2012; Volkow et al., 2012). Ae ui i lea, o mea taua e tuʻuina atu ai le faʻafitauli i le faʻalogoina e mafai ona fegalegaleai ma le faʻatulagaina o tala faʻasolopito e faʻamalosia ai aʻafiaga o taui e leʻi fuafuaina (ie, 50% CS-US faʻasologa) i luga o le faʻaogaina o le polokalama. Mo le su'esu'eina o lenei avanoa, o le fa'ata'ita'iga 3 na fa'aogaina le faiga lava e tasi e pei o le fa'ata'ita'iga 2 ae fa'aaoga le Lewis strain nai lo Sprague Dawley strain rats.
Sprague Dawley rats display intermediate levels of DA transporters, with lower levels than Wistar strain rats (Zamudio et al., 2005), but higher levels than Wistar-Kyoto rats (a “depressive”-like strain) in the nucleus accumbens, amygdala, ventral tegmental area and substantia nigra (Jiao et al., 2003). This profile may render Sprague Dawley rats only moderately sensitive to environmental or pharmacological manipulations of DA function. In contrast, Lewis rats exhibit low levels of DA transporters as well as D2 and D3 DA receptors in the nucleus accumbens and dorsal striatum compared to other strains (e.g., F344) (Flores et al., 1998). These morphological differences may contribute to Lewis rats’ differential response to DA manipulations. Lewis rats also exhibit a range of accentuated responses to experimental drug manipulations compared to other strains (e.g., F344). Most importantly, Lewis rats display greater sensitization to methamphetamine, characterized by low response to initial doses but higher response to later doses (Camp et al., 1994). Lewis rats also exhibit greater locomotor sensitization to a range of doses of cocaine (Kosten et al., 1994; Haile et al., 2001). Faʻavae i luga o lenei faʻataʻitaʻiga o aʻafiaga, matou te manatu o le Lewis rats e mafai ai ona matou suʻesuʻeina pe o le faʻafefe i le faʻalogoina e faʻateleina ai aʻafiaga o le faʻatulagaina o faʻatulagaga i le tali mulimuli ane i le AMPH.
Faʻamatalaga 3
Mea ma Metotia
O le auala e tutusa ma le faʻataʻitaʻiga 2, e ese mai le faʻaaogaina o Lewis rats (200-225 g i le taunuu mai, Charles River, Quebec, Kanata).
i'uga
Tu'i isu ile taimi ole sucrose conditioning
A 5 Vaega × 15 Sauniga × 2 Vaega (CS o loʻo i ai, CS toesea) ANOVA o tui isu na maua ai aʻafiaga autu taua ole Vaega, F(4, 34) = 6.12, p = 0.001, Sauniga, F(14, 476) = 3.42, p <0.001, ma le Vaega, F(1, 34) = 20.83, p <0.001, faʻapea foʻi ma se fesoʻotaʻiga taua e tolu-auala, F(56, 476) = 1.56, p = 0.008. Panela (A, B) o Ata 7 Fuafua fa'ailoga tu'i isu a vaega mo le CS o lo'o iai ma le CS toesea, fa'asologa. Fa'atusatusaga o paneli e lua e fa'aalia ai o le a'afiaga autu o le Vaega na atagia mai ai le tele o tali tu'i isu pe a iai le CS vs. O le mea lea, o tali fa'alogo na tupu tele tele nai lo tali a'o le'i matua. O a'afiaga autu o le Vaega ma le Sauniga e le'i faigofie ona fa'amatalaina ona o le fa'atonuga maualuga. O fegalegaleaiga e tolu-auala na atagia mai ai le fefiloi o togi mo vaega e lima i se tulaga maualalo mautu i le va o vasega pe a toesea le CS [Panel. (B)], faʻatasi ai ma se eseesega o togi pe a iai le CS i ni faʻamatalaga tuʻufaʻatasia mo vaega taʻitasi e faʻatusalia a latou faʻasologa o faʻasologa o taui: mai le maualuga (vaega 100) i lalo (vaega 25) [Panel. (A)]. Na'o le laina laina mo fegalegaleaiga sa taua, F(4, 34) = 4.03, p = 0.009, e atagia ai le faʻateleina o le faʻateleina o le isu i luga o vasega i le vaega 100 ina ua i ai le CS e faʻasaga i le faʻalavelave le tutusa o le faʻatupulaia o isu isu i vasega i isi vaega i lenei vaega.
Figure 7. Mean (SE) approach responses (nose pokes) on 15 sucrose training sessions in groups of Lewis rats (n = 8 / vaega) faʻaalia i le sucrose taui (10% solution) tuʻuina atu i lalo ole 0, 25, 50, 75, poʻo le 100% faʻasologa o suiga. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. (A) Scores when CS was present (5 s × 20 trials). (B) Scores when CS was absent (average for 5 × 20 s while light was off).
Mauaina i pusa locomotor
O le 5 Group × 3 Session ANOVA na maua ai se aafiaga autu o le Sauniga, F(2, 70) = 23.07, p <0.0001, ma e leai se isi aafiaga taua, F(8, 70) <1.47, p > 0.18. Na alia'e mai le fa'asologa 1, 1076 (74), i le vasega 2, 644 (48), i le vasega 3, 762 (59) se fa'asologa fa'asolosolo o le uiga (SE) locomotor. O fa'atusatusaga fuafuaina o le vaega 50 ma le vaega 0 ma le vaega 100 i le ulua'i ma le fa'ai'uga o fa'atasiga na fa'aalia ai le itiiti ifo o le va'a o le ave i le vaega 50 (M = 911; SE = 109) vs. vaega 0 (M = 1103; SE = 176) i le sauniga masani 1, t(105) = 2.02, p <0.05, ae leai se eseesega i le va o le vaega 50 ma le vaega 100 (M = 1066; SE = 150), t(105) <1.20, p > 0.20, i lenei vasega. Vaega 50 e leai se eseesega tele mai le vaega 0 poʻo le vaega 100 i le faʻasalaga mulimuli, t(105) <0.93, p > 0.30. Ole mea lea, ole tali ole locomotor e leai ni vaila'au i vaega autu e le'i eseese i taimi uma a'o le'i faia su'ega.
Su'ega vasega
Saline. O le 5 Group × 2 Session ANOVA o tali o locomotor i luga o le faʻasalalauga mulimuli ma le suʻega saline na maua ai se aafiaga taua tele o le Sauniga, F(1, 35) = 50.12, p <0.0001, ma e leai se isi aafiaga taua, F(4, 35) <0.57, p > 0.68. Ata 8 o lo'o fa'aalia ai le aofa'i o togi o vaega mo vasega e lua ma fa'ailoa mai o le a'afiaga o le Sauniga na atagia mai ai le fa'aitiitia tele mai le masani i le su'ega saline. O lea la, mauaina o le tui taʻitasi (fa'ata'ita'iga, fa'amoemoe, fa'alavelave) e le'i fa'aleleia le tali atu o locomotor.
Figure 8. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) on the last of 3 drug-free habituation sessions and on a subsequent session after saline injection (i.p., 1 ml/kg) in groups of Lewis rats (n = 8/group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, 75, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli.
Aafiaga ole 0.5 mg/kg AMPH.
A'o le'i tui tui. A 5 Vaega × 2 Sauniga ANOVA o locomotion muai tui na maua ai se aafiaga autu taua o le Sauniga, F(1, 35) = 15.04, p <0.001, ma e leai se isi aafiaga taua, F(4, 35) <1.19, p > 0.33. O faʻatusatusaga fuafuaina e leai se eseesega tele i le va o le vaega 50 ma le vaega 0 poʻo le vaega 100 i luga o suʻega suʻega, t(70) <0.99, p > 0.30. O le mea lea, o eseesega faʻavae i le locomotion aʻo leʻi tuiina e leʻi faʻamatalaina le eseesega o vaega i le tali a le locomotor i le 0.5 mg / kg AMPH. Mean (SE) vaeluaga mo le vaega muamua o tui mo le muamua ma le lona lua (post-sensitization) 0.5 mg / kg sauniga o 325 (25) ma le 473 (36).
Fa'ato'a tui. A 5 Vaega × 2 Sauniga ANOVA o locomotor tali i le 0.5 mg / kg doses tuʻuina atu aʻo leʻi maeʻa ma pe a uma le 1 mg / kg AMPH masani na maua ai se aafiaga autu o le Sauniga, F(1, 34) = 87.44, p <0.0001, ma e leai se isi aafiaga taua, F(4, 34) <0.94, p > 0.45. Ata 9 fa'afuafua le aofa'i o sikoa locomotor mo vaega ta'itasi ma vasega ma fa'aalia ai o le a'afiaga o le Sauniga na atagia mai ai le fa'atuputeleina o le tali atoa i le fua lona lua o le 0.5 mg/kg, fa'atasi ma le fa'alogoina. O loʻo faʻaalia foi e le faʻatusa o vaega na faia tutusa i le vasega 1, ae o le vaega 50 na faʻaalia le tele o gaioiga o locomotor nai lo isi vaega i le vasega 2. Faʻatusatusaga fuafuaina i le tali atu i le 0.5 mg / kg dose muamua na faʻaalia ai le leai o se eseesega tele i le va o le kulupu 50 ma vaega 0 po'o le vaega 100, t(35) <1.28, p > 0.20. Ae ui i lea, o le vaega 50 na faʻaalia le tele o le tali atu o locomotor i le 0.5 mg / kg lona lua nai lo le vaega 0, t(35) = 4.32, p <0.001, po'o le vaega 100, t(35) = 2.24, p <0.05.
Figure 9. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) to 0.5 mg/kg d-amphetamine on separate sessions before and after a 5-session sensitizing regimen of d-amphetamine (1.0 mg/kg; i.p. per session) in groups of Lewis rats (n = 8/group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, 75, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. *p < 0.05 for mean difference between group 50 and group 0 as well as group 100, based on planned comparisons.
Aafiaga ole 1 mg/kg AMPH.
A'o le'i tui tui. O le 5 Group × 5 Session ANOVA o le 30-min pre-injects scores mo le faʻalauiloaina o sauniga na maua ai se aafiaga autu o le Sauniga, F(4, 140) = 4.10, p = 0.004, ma e leai se isi aafiaga taua, F(4, 35) = 1.25, p > 0.31. O faʻatusatusaga fuafuaina na maua ai le gau o le uila i le taimi muamua o le tui (M; SE) na matua maualalo i le vaega 50 (395; 62) nai lo le vaega 100 (508; 62), t(175) = 2.58, p <0.01, ae le o le vaega 0, t(175) <1.83, p > 0.10, i luga o le 1 mg / kg AMPH sauniga 1. I luga o le 1 mg / kg AMPH sauniga mulimuli, fuafuaina faʻatusatusaga na maua ai foi o locomotion muai tui i le vaega 50 (378; 60) na matua maualalo ifo nai lo le vaega 100 (650; 75). ), t(175) = 6.17, p <0.001, ae le o le vaega 0, t(175) <1.84, p > 0.10. Talu ai o le faʻatonuga o nei eseesega vaega (vaega pulea = vaega 50) sa faʻafeagai ma le faʻataʻitaʻiga faʻataʻitaʻiga, o le eseesega o kulupu i le post-injection locomotion e ogatusa ma le manatu e le mafai ona faʻatatau i le eseesega o le laina muamua. Mean (SE) fa'ato'a motu o ave i le taimi a'o le'i tui mo le Vaega 1 e o'o i le 5: 442 (34), 452 (32), 542 (40), 411 (26), 504 (37).
Fa'ato'a tui. A 5 Group × 5 Sessions ANOVA o tali i le 1 mg / kg doses na maua ai se aafiaga taua tele o le Sauniga, F(4, 140) = 6.15, p <0.001, ma e leai se isi aafiaga taua, F(4, 35) <0.57, p > 0.68. O su'esu'ega a le Polynomial na fa'aalia ai se fa'asologa tele o laina, F(1, 35) = 9.34, p = 0.004, ma le tulaga kupita, F(1, 35) = 5.08, p = 0.031, o le fa'ai'uga mulimuli o lo'o fa'aalia ai le maualuga maualuga i vasega 3 ma le 5. Ata. 10 fa'ailoga nei togi ma fa'aalia ai, e ui lava i le leai o se feso'ota'iga taua i le ANOVA, o le vaega 50 na fa'aalia le tele o locomotion nai lo isi vaega e fa i le tali atu i le fa'ai'uga mulimuli 1 mg/kg. E tusa ai, o faʻatusatusaga fuafuaina na faʻaalia ai le sili atu o le maualuga o togi i le vasega 5 i le vaega 50 nai lo isi vaega uma, t(35) > 3.68, p <0.001.
Figure 10. Mean (SE) locomotor response (number of beam breaks in an electronic array per 90 min) to 1 mg/kg d-amphetamine (i.p.) on 5 weekly sessions in groups of Lewis rats (n = 8/group) previously exposed to 15 daily conditioning sessions with sucrose reward (10% solution) delivered under 0, 25, 50, 75, or 100% variable schedules. The conditioned stimulus was a light (120 s). Group 0 received the same number of rewards as group 100 in the absence of conditioned stimuli. *p < 0.05 for mean difference between group 50 and group 0 as well as group 100, based on planned comparisons.
Puleaina mo le fesuisuiai o le tali atu o tui isu i le taimi o aoaoga sucrose
Lua 5 Vaega × 2 Session ANCOVAs o locomotor tali i le 0.5 mg / kg AMPH aʻo leʻi faia ma pe a maeʻa le faʻaogaina o le faʻaogaina, e aofia ai le aofaʻi o le isu i le taimi o aʻoaʻoga sucrose ma le CS o loʻo i ai ma le CS o loʻo toesea o ni mea eseese, e leai ni aʻafiaga taua mo soʻo se tasi, F(1, 32) <0.44 p > 0.51. Lua 5 Group × 5 Session ANCOVAs o le tali a locomotor i le 1 mg / kg AMPH i le taimi o faʻasalalauga faʻatasi ma le aofaʻi o le isu (CS o loʻo i ai, CS toesea) ona o faʻasalalauga eseese e leai ni aʻafiaga taua o le covariate aʻo iai le CS pe toesea, F(1, 33) <0.14, p > 0.71. O le mea lea, o le tali atu e leai ni vailaʻau e leʻi faʻamatalaina mo eseesega o vaega i tali o locomotor i soʻo se fua ole AMPH.
Talanoaga
Sensitization developed to the effects of repeated 1.0 mg/kg amphetamine. The habituation and saline data confirm that this effect was not due to pre-existing differences, expectancy, or stress-related responses to the injection. The ANCOVAs with nose pokes confirm that these effects were not due to drug-free approach behavior. The nose poke data themselves indicated that the groups acquired the association between the CS and prospect of sucrose reward. The groups’ rank level of nose-poke responding at the end of training matched the overall frequency of reward under the different schedules from highest (group 100) to lowest (group 0), as it did in experiment 2. The relatively lower overall mean nose poke levels in this experiment compared to experiments 1 and 2 may reflect more selective approach responding to cues for reward in Lewis rats (Kosten et al., 2007).
O le 0.5 mg / kg faʻamaumauga o faʻamaumauga na faʻaalia ai le tali muamua o le locomotor i le AMPH i Lewis rats (Ata 9) sa fai si taofiofia pe a faatusatusa i iole Sprague Dawley (fa'ata'ita'iga 2; Ata 5), ae o le siʻitia i totonu o le kulupu i le tali atu i le fua lona lua i Lewis rats na tele (toetoe faʻaluaina le tali i le 0.5 mg / kg muamua dose) i le maeʻa ai o le 5-session AMPH regimen O le mea sili, o le vaega 50 na faʻaalia se tali sili atu o locomotor. nai lo vaega uma sei vagana ai le vaega 25 i le lona lua (ie, post-sensitization) 0.5 mg/kg AMPH dose ma sili atu le tali atu o locomotor nai lo isi vaega uma, e aofia ai le kulupu 25, i le 1 mg/kg AMPH dose mulimuli (fa'ai'uga fa'alogoina taimi) .
Otootoga au'ili'ili o fa'avasegaga fa'avasega i fa'ata'ita'iga
To determine the reliability of group differences in sensitization, a non-parametric analysis assessed the contingency between group and rank of mean locomotor response to the second (post-chronic AMPH) 0.5 mg/kg dose and the final 1.0 mg/kg dose of AMPH from the 3 experiments. The analysis yielded a significant effect, φ = 0.986, p = 0.025, e atagia ai le mea moni o le vaega 50 o loʻo tulaga muamua i mea uma ae o le tasi o faʻatusatusaga. O le tulaga maualuga o le vaega 50 faʻatusatusa i isi vaega uma i le tali atu i le lona lua (post-chronic AMPH) 0.5 mg / kg dose o loʻo faʻaalia i le Ata. 5 (fa'ata'ita'iga 2) ma le Ata 9 (fa'ata'ita'iga 3). O le maualuga maualuga o le vaega 50 e faʻatatau i isi vaega i le tali atu i le 1.0 mg / kg faʻaiʻuga mulimuli o loʻo faʻaalia i le Ata. 2 (fa'ata'ita'iga 1) ma le Ata 10 (fa'ata'ita'iga 3). Pau lava le tuusaunoaga i lenei mamanu o le tali atu i le 1.0 mg / kg faʻaiʻuga mulimuli i Sprague-Dawley rats i le faʻataʻitaʻiga 2.
Lautele Talanoaga
The present series of experiments tested the hypothesis that chronic exposure to a gambling-like schedule of reward can sensitize brain DA pathways much like chronic exposure to drugs of abuse. Evidence for such an effect would suggest that neuroplasticity, of the same kind thought to contribute to drug addiction, can be induced by chronic exposure to unpredictable reward schedules. In line with the literature on drug addiction, locomotor response to 0.5 and 1.0 mg/kg doses of AMPH indexed DA system reactivity, with greater locomotion in response to later doses operationally defining sensitization (cf. Robinson ma Berridge, 1993; Pierce ma Kalivas, 1997; Vanderschuren ma Kalivas, 2000).
I le aotelega, o fa'ai'uga o lo'o o gatasi ma lo tatou manatu. Ae ui i lea, latou te faʻaalia foi le tele o fesuiaiga i aafiaga faʻataʻitaʻiga ona o mea taua. O aʻafiaga o faʻatulagaga faʻatulagaina e tauagafau ae tumau, faʻatasi ai ma le kulupu 50 o loʻo faʻaalia le tali sili atu nai lo isi vaega e fa i tui uma e lua pe a maeʻa le lima dose-regimen. E ui ina lautele F-taua mo aʻafiaga e fesoʻotaʻi vaega i le vaʻaiga o eseesega e masani lava e le taua, o eseesega vaega autu na faʻamaonia ma faʻatusatusaga fuafuaina. I lenei tulaga e tatau ona matauina e faapea, “Ae ui i lea, o mafaufauga i le taimi nei, o le taua atoa lena [mo F i le ANOVA] e le manaʻomia. Muamua lava, o manatu na faʻataʻitaʻiina e le suʻega atoa ma se suʻega faʻatusatusaga e tele e matua ese lava, ma e ese le maualuga o le mana. Mo se faʻataʻitaʻiga, o le aotelega F fa'asoa moni lava eseesega i vaega i le numera o tikeri o le sa'olotoga mo vaega. E i ai le a'afiaga o le fa'aitiitia o le aotelega F in the situation where several group means are equal to each other but different from some other mean” (Howell, 1992, i. 338). O le tulaga tonu lea na faʻaaogaina i suʻesuʻega o loʻo i ai nei, lea na faʻamoemoeina le kulupu 50 e ese mai le kulupu 0 ma le kulupu 100 faʻatonutonu ae leai se eseesega i le va o nei vaega faʻatonutonu na valoia mo le vaega 25 poʻo le vaega 75.
O faʻamaumauga o le isu na faʻamaonia ai, i suʻesuʻega uma, na maua e manu le fesoʻotaʻiga i le va o le CS ma le faʻamoemoe o le taui sucrose. O le fesoʻotaʻiga i le va o le isu e tuʻi taimi mo vaega eseese ma le tele o taimi o taui i lalo oa latou faʻasologa o aʻoaʻoga e taʻu mai ai o le averesi o le sucrose taui e taʻitaʻia ai le leai o se fualaau faasaina. Ae ui i lea, o le leai o se faʻasalalauga aʻafiaga o le isu o loʻo i luga o tali o locomotor e fesoʻotaʻi ma vaega i le AMPH i le ANCOVAs na faʻaalia ai o faiga eseese e faʻavae ai amioga e lua.
I nisi tulaga, o le aʻafiaga o le faʻatulagaina o faʻatulagaga na faʻaalia i le tali atu i le muamua AMPH dose; i isi tulaga e na'o le alia'e mai pe a uma ona fai fa'asolo. O le eseesega o vaega i le tali a le locomotor i le muamua AMPH dose o loʻo fautua mai ai o le faʻaalia i faʻasologa o taui e pei o taaloga faitupe e lava lava e faʻaosofia ai le lagona. O le eseesega o vaega i le gaioi pe a mae'a le tele o tui AMPH ua fa'ailoa mai ai se a'afiaga e sili atu ona maaleale e mafai ona fa'ailoaina o le "mafaufau," lea e fa'aalia pe a tu'ufa'atasia ma le fa'aauau pea ona fa'aalia i le mea e fa'amamafaina ai (ie, amphetamine).
Differences in the pattern of response across experiments suggest that a longer interval between training and initial AMPH challenge may maximize the opportunity to detect the inherent sensitizing effect of the conditioning treatment. This in turn suggests that effects of conditioned reward exposure may incubate over time, a phenomenon also seen with stimulant sensitization (Grimm et al., 2006). O le faʻataʻitaʻiga o le tali atu i tui e lua o le amphetamine e taʻu mai ai o le 0.5 mg / kg dose atonu e sili atu le aoga i le faʻaalia o aʻafiaga o le faʻatulagaina o talafaasolopito. O le mea lea e taʻu mai ai o aʻafiaga faʻatulagaina i lalo o le faʻasologa o aʻoaʻoga o loʻo i ai nei e fai si maaleale ma e mafai ona faʻapipiʻiina e aʻafiaga o le taualuga i lalo o tui o le AMPH ma tulaga e faʻatupuina. de novo lagona.
In experiment 3, the biphasic pattern of response to the 0.5 mg/kg doses and progressive emergence of superiority in group 50 is consistent with the expected profile for Lewis rats in response to methamphetamine (Camp et al., 1994). O lenei mea e tuʻuina atu ai le lagolago i le faʻamaonia o suʻesuʻega o loʻo i ai nei ma faʻaalia ai le felafolafoaʻi i le va o mea taua e faʻafefe ai le faʻaogaina o le psychostimulant sensitization ma i taaloga faitupe-pei o taimi o taui.
Across experiments, the post-sensitization locomotor response of group 50 generally exceeded that of the other groups under different doses of amphetamine and in different strains of animals. However, the high within-group variability and modest between-group effect sizes indicate a role for other factors in DA system reactivity to amphetamine following exposure to varying schedules of conditioned sucrose reward. Although responses of DA neurons to reward signals may provide a coarse model of gambling (Fiorillo et al., 2003), pei o faʻataʻitaʻiga uma, o loʻo i ai le leiloa o faʻamatalaga mo le lelei o le parsimony-ie, e faʻaalia ai se faʻagasologa autu. O se taunuuga, o le mamanu o aʻafiaga i luga o tulaga CS-US i le uluai Fiorillo et al. O su'esu'ega e le'o fa'asalalau atoa ile tali ole locomotor ile amphetamine. O isi fa'aleleia atili o le fa'ata'ita'iga e mana'omia ina ia pu'e atoatoa vaega o taaloga faitupe e a'afia ai le fa'atinoga o le faiga a le DA.
Taken together, the results of this series of experiments provide provisional support for the hypothesis that chronic exposure to gambling-like schedules of reward enhances the reactivity of the brain DA system to psychostimulant challenge. As such, they extend the findings of Singer et al. (2012) who demonstrated that, relative to a fixed schedule, prior exposure to a variable reinforcement schedule in an operant paradigm enhances subsequent locomotor response to amphetamine. More specifically, the present findings point to uncertainty of reward delivery as the critical factor underlying the effects of variable reward. The magnitude of effects in the operant paradigm was substantially greater than the effects found in the present experiments. This may reflect greater chronic exposure to the gambling-like activity (55 vs. 15 days); it may reflect the effects of requiring an operant response to elicit the reward (i.e., a role for agency) rather than passive exposure, as in the present study. Increasing the duration of training in the present paradigm would help to resolve these questions.
The validity of variable reward and reinforcement schedules as models of gambling cannot be gleaned from these experiments. Future research that examines the impact of conditioning history on risk-taking behavior in rodent gambling tasks could address this issue. Similarly, the correspondence between the behavioral sensitization found here and the elevated striatal DA response to amphetamine recently found in pathological gamblers must await further investigation (Boileau et al., 2013). Micro-dialysis e mafai ona taliina lenei fesili, ma o le valoʻaga e faʻavae i luga o faʻamatalaga a le tagata o le a sili atu le tuʻuina atu o le DA i le vaega 50 "gamble phenotype" o le a sili ona manino ona matauina i le pito i tua (sensorimotor) striatum nai lo le ventral (limbic) striatum. . O le faʻamaoniaina o le 50% fesuiaiga CS + faʻaalia taui i isi faʻataʻitaʻiga o le a lagolagoina lona aoga e avea o se faʻataʻitaʻiga faʻataʻitaʻiga faʻamaonia o le PG.
Whereas some forms of gambling clearly entail an instrumental response (e.g., slot machines), in other forms of gambling (e.g., lottery) the link between the action (purchasing the ticket, i.e., placing the bet), the cues for reward (i.e., lottery numbers) and the reward itself (the winning number and monetary payoff) is much more diffuse. Nevertheless, activation of DA during the CS-US interval may well occur. This may explain why, when the “winning number” is announced, attention is riveted as each individual lottery ball drops in succession to compose the specific sequence of digits in the winning number. Although the probability of a specific digit occurring is mathematically defined, the outcome for each individual lottery ball is binary—hit (matches the player’s number) or miss (does not match the player’s number)—and the outcome on any given trial is unknown. Such a scenario may better characterize the experience of group 50 in the present experiments, where reward was provided non-contingently but also unpredictably and the CS merely indicated the potential for reward without revealing whether it would occur on a given trial. Slot machines are more strongly linked with PG than are lottery tickets (Cox et al., 2000; Bakken et al., 2009), indicating an important role for instrumental factors (and immediacy) in the rewarding aspects of gambling for this population (Loba et al., 2001). Ae ui i lea, o le faiga Pavlovian faʻataʻitaʻiina i faʻataʻitaʻiga o loʻo i ai nei (CS + le mautinoa taui) e foliga mai e manaʻomia pe a le lava le elemene o le poto masani i taaloga faitupe.
Faatasi ai ma le leai o se mea faigaluega manino manaʻomia, o le tele o isi faʻataʻitaʻiga foliga atonu na saofagā i le faʻataʻitaʻiga faʻalelei ma le fesuisuiai o faʻataʻitaʻiga. O vaega na eseese i le lautele o le sucrose faʻaalia faʻapea foʻi ma le faʻalavelave i le va o le CS ma le taui sucrose. E ui lava atonu na saofagā lenei mea i le felafolafoaʻi o vaʻaiga, e le mafai ona faʻamatalaina pe aisea e faʻaalia ai e manu e sili atu le sucrose (vaega 100) faʻaalia le faʻaitiitia o lagona nai lo le vaega 50. E le gata i lea, o le vaega 0 e leʻi maua se faʻamalosi aʻo leʻi faʻaalia le sucrose i tofotofoga uma. E ui lava o lenei mea na taofia ai le faʻamoemoeina o le taui, e leʻi pulea le i ai o se faʻamalosi aʻo leʻi tuʻuina atu taui, lea sa i ai i isi vaega uma. Ina ia foia lenei mataupu, o suʻesuʻega i le lumanaʻi e tatau ona aofia ai se tulaga e maua ai e manu le taui i faʻataʻitaʻiga uma pe a maeʻa faʻaalia i se faʻalavelave faʻafefe (faʻataʻitaʻiga, o lona i ai e le faʻaalia ai le avanoa mo se taui).
Another design limitation is the potential emergence of adjunctive behavior that could influence the effects of training schedule. In the face of uncertainty, animals may develop superstitious behaviors designed to enhance perceived control and reduce uncertainty-induced DA activation (cf. Harris et al., 2013). O le mea lea e ono mafai ai e vaega le pulea o le faʻataʻitaʻiga faʻataʻitaʻiga na mafai ai e manu ona faʻafefe aʻafiaga o le faʻatulagaina o faʻatulagaga. O sea aafiaga e mafai ona saofagā i le tali tausaafia ma le fesuisuiai o le amphetamine i le vaega 50 pe a maeʻa aʻoaʻoga CS + sucrose. O su'esu'ega i le lumana'i e tatau ona fa'amaumau amioga fa'afuase'i, se'i vagana ai tu'i isu, i taimi o toleniga e fa'ata'ita'i ai lenei avanoa, ma fa'atonutonu fua fa'atatau pe a tula'i mai. Talu ai ona o ia amioga o le a faʻamoemoeina e faʻafefe pe faʻavaivaia ai aʻafiaga o le le mautonu e mafua mai i le faasologa, o le tali atu o locomotor i le amphetamine i le vaega 50 e tatau ona faʻaleleia pe a faʻatonutonuina (faʻasologa poʻo fuainumera). O le mea lea, o le taimi nei (le pulea) mamanu e maua ai se suʻega faʻamaonia o aʻafiaga o le 50% CS + taui i luga o le amphetamine sensitization.
In terms of external validity, the use of male rats also limits the generalizability of the results. The lack of a clear “punishment” condition also differs from gambling, where large monetary losses are common and exert important motivational effects (Nieuwenhuis et al., 2005; Singh and Khan, 2012). The ability to accumulate reward is also absent from the present paradigm and cumulative winnings in a slot machine game have been found to interact with DA manipulations in humans (Tremblay et al., 2011; Smart et al., 2013). E faapena foi, o le avanoa mo se jackpot o se eseesega taua i le va o le faʻataʻitaʻiga nei ma taaloga faitupe moni.
Despite these limitations, the present results suggest that 50% variable CS + reward can engage DA pathways implicated in the reinforcing effects of gambling (Fiorillo et al., 2003; Anselme, 2013). Cross-sensitization of response to AMPH following this gambling-like schedule is consistent with a pivotal role for DA in gambling and psychostimulant drug effects (Zack ma Poulos, 2009), and extends earlier studies on cross-priming of motivation to gamble by AMPH in pathological gamblers (Zack ma Poulos, 2004). The present results also indirectly suggest that modest doses of AMPH, which do not cause supra-physiological DA release, may better model brain activity in response to intermittent reward signals (i.e., during gambling) than exposure to high (i.e., binge-like) doses of stimulant drugs (cf. Vanderschuren ma Pierce, 2010). E mafai ona maua le lagolago tuusaʻo mo lenei fesoʻotaʻiga e ala i le suʻesuʻeina o le tuʻuina atu o le DA i le tali atu i le 50% fesuiaiga CS-US faʻasologa ma faʻasologa eseese o le AMPH e faʻaaoga ai le microdialysis.
Mai se fa'ata'ita'iga fa'ata'ita'iga, o le fa'ata'ita'iga Pavlovian o lo'o iai nei ma le fa'ata'ita'iga muamua o le fa'amalositino fa'aopoopo e foliga mai e fa'atupuina ai se fa'ata'ita'iga e pei o le tagata gambler pathological. O lea la, latou te maua ai se fesoasoani taua i galuega faitupe iore e fa'ata'ita'i ai amioga tau tupe (o se fua fa'alagolago) ae e o'o mai i le taimi nei, na'o le fa'afaigaluegaina o manu ola maloloina, e tutusa ma tagata ta'alo gamblers. Faʻavae i luga o tusitusiga, o manu e masani ona faʻaalia i taui fesuiaʻi atonu e eseese i nei galuega, aemaise lava i le tali atu i vailaʻau DA-ergic. O le tu'ufa'atasia o le fa'ailoga o taaloga iole ma galuega tau tupe e mafai ona fa'ataga ai le fa'atupuina o vaila'au mo togafitiga o le PG, atonu e le mafai ona fa'ataunu'uina na'o manu ola maloloina. O isi faʻaleleia atili i le faʻataʻitaʻiga faʻataʻitaʻiga ma aʻoaʻoga, e pei ona faʻamatalaina i luga, e tatau ona faʻaleleia atili le fesoʻotaʻiga i le va o manu ua aʻoaʻoina i lenei faʻataʻitaʻiga ma tagata taʻavale moni.
From the clinical-sociological standpoint, the finding that exposure to 50% variable CS + reward, which closely matches the reward schedule on a commercial slot machine (Tremblay et al., 2011), suia le faiʻai DA faiga i auala faʻatuatuaina ma tumau e taʻu mai ai, i nisi tulaga, gaioiga o taaloga faitupe, e pei o vailaʻau o le faʻaleagaina, atonu o se "patogen" e mafai ona mafua ai vaisu. Ae ui i lea, o le laititi o le aʻafiaga o le tele ma le maualuga o le fesuiaiga i le tali atu i le 50% CS + taui o loʻo fautua mai ai, e pei o vailaʻau o le faʻaleagaina, o le faʻaogaina o faʻasologa o taui e pei o taaloga faitupe e faʻalauteleina ai vaisu o le a faʻalagolago tele i le tulaga lamatia o loʻo i ai muamua a le tagata taalo. Ae ui i lea, ina ia fa'asaoina tagata ta'ito'atasi maualuga le ono a'afia i a'afiaga leaga e feso'ota'i ma taaloga faitupe, e foliga mai e talafeagai le fa'aogaina o faiga fa'avae e taofia ai le fa'aogaina ma fa'aitiitia ai le fa'aleagaina mai fualaau fa'asaina e mafai ona fa'alautele atu i taaloga faitupe.
Feteʻenaʻiga o Tupulaga e Tetee ai
Fai mai tusitala o le suʻesuʻega sa faia i le leai o soʻo se fefaʻatauaʻiga faʻapisinisi pe tau tupe e mafai ona avea o se feteenaʻiga e ono aʻafia ai.
tautinoga
O lenei su'esu'ega sa fa'atupeina e fesoasoani mai le The Natural Sciences and Engineering Research Council of Canada ia Paul J. Fletcher. Matou te faafetai atu ma le faamaoni ia Ms. Djurdja Djordjevic mo le sauniaina o fuainumera.
mau faasino
Anselme, P. (2013). Dopamine, faaosofiaga, ma le taua o le evolusione o amioga pei o taaloga faitupe. Faʻatasi. Brain Res. 256, 1-4. Pule: 10.1016 / j.bbr.2013.07.039
A.P.A. (2013). Fuainumera Faʻamau ma Fuainumera Faʻamaumauga o Manatu o Mafaufauga, 5th Edn. Arlington, VA: American Psychiatric Publishing.
Bakken, I. J., Gotestam, K. G., Grawe, R. W., Wenzel, H. G., and Oren, A. (2009). Gambling behavior and gambling problems in Norway 2007. Scand. J. Psychol. 50, 333-339. Pule: 10.1111 / j.1467-9450.2009.00713.x
Boileau, I., Payer, D., Chugani, B., Lobo, D. S., Houle, S., Wilson, A. A., et al. (2013). I vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [C]-(+)-PHNO. Mol. Fomaʻi doi: 10.1038/mp.2013.163. [Epub ahead of print].
Bolles, R. C. (1972). Reinforcement, expectancy, and learning. Toma. Faaa. 79, 394–409. doi: 10.1037/h0033120
Camp, D. M., Browman, K. E., and Robinson, T. E. (1994). The effects of methamphetamine and cocaine on motor behavior and extracellular dopamine in the ventral striatum of Lewis versus Fischer 344 rats. Brain Res. 668, 180–193. doi: 10.1016/0006-8993(94)90523-1
Conversano, C., Marazziti, D., Carmassi, C., Baldini, S., Barnabei, G., and Dell’Osso, L. (2012). Pathological gambling: a systematic review of biochemical, neuroimaging, and neuropsychological findings. Harv. Rev. Psychiatry 20, 130-148. Pule: 10.3109 / 10673229.2012.694318
Cox, B. J., Kwong, J., Michaud, V., and Enns, M. W. (2000). Problem and probable pathological gambling: considerations from a community survey. E mafai. J. Fomaʻi 45, 548-553.
Dalley, J. W., Theobald, D. E., Eagle, D. M., Passetti, F., and Robbins, T. W. (2002). Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex. Neuropsychopharmacology 26, 716–728. doi: 10.1016/S0893-133X(01)00412-2
Everitt, BJ, ma Robbins, TW (2005). Auala faʻavaomalo o le faʻamalosia mo le tagofiaina o vailaau faʻasaina: mai gaioiga i masaniga faʻamalosi. Nat. Neurosci. 8, 1481-1489. doi: 10.1038 / nn1579
Fiorillo, CD, Tobler, PN, ma Schultz, W. (2003). Faʻapitoa faʻasologa o le taumatemateina o le tau ma le le mautinoa e dopamine neurons. saienisi 299, 1898â € "1902. doi: 10.1126 / science.1077349
Flagel, S. B., Watson, S. J., Akil, H., and Robinson, T. E. (2008). Individual differences in the attribution of incentive salience to a reward-related cue: influence on cocaine sensitization. Faʻatasi. Brain Res. 186, 48-56. Pule: 10.1016 / j.bbr.2007.07.022
Fletcher, P. J., Tenn, C. C., Rizos, Z., Lovic, V., and Kapur, S. (2005). Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Psychopharmacology (Berl.) 183, 190–200. doi: 10.1007/s00213-005-0157-6
Flores, G., Wood, G. K., Barbeau, D., Quirion, R., and Srivastava, L. K. (1998). Lewis and Fischer rats: a comparison of dopamine transporter and receptors levels. Brain Res. 814, 34–40. doi: 10.1016/S0006-8993(98)01011-7
Frascella, J., Potenza, M. N., Brown, L. L., and Childress, A. R. (2010). Shared brain vulnerabilities open the way for nonsubstance addictions: carving addiction at a new joint? Ann. NY Acad. Sci. 1187, 294-315. Pule: 10.1111 / j.1749-6632.2009.05420.x
Grimm, J. W., Buse, C., Manaois, M., Osincup, D., Fyall, A., and Wells, B. (2006). Time-dependent dissociation of cocaine dose-response effects on sucrose craving and locomotion. Faʻatasi. Pharmacol. 17, 143–149. doi: 10.1097/01.fbp.0000190686.23103.f8
Haile, C. N., Hiroi, N., Nestler, E. J., and Kosten, T. A. (2001). Differential behavioral responses to cocaine are associated with dynamics of mesolimbic dopamine proteins in Lewis and Fischer 344 rats. Synapse 41, 179–190. doi: 10.1002/syn.1073
Harris, J. A., Andrew, B. J., and Kwok, D. W. (2013). Magazine approach during a signal for food depends on Pavlovian, not instrumental, conditioning. J. Exp. Toma. Manu. Faʻatasi. Faʻamasinoga. 39, 107-116. doi: 10.1037 / a0031315
Howell, D. C. (1992). Statistical Methods for Psychology. Boston, MA: Duxbury.
Ito, R., Dalley, J. W., Robbins, T. W., and Everitt, B. J. (2002). Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of a drug-associated cue. J. Neurosci. 22, 6247-6253.
Jiao, X., Pare, W. P., and Tejani-Butt, S. (2003). Strain differences in the distribution of dopamine transporter sites in rat brain. Prog. Neuropsychopharmacol. Biol. Fomaʻi 27, 913–919. doi: 10.1016/S0278-5846(03)00150-7
Koob, G. F., and Le Moal, M. (2008). Review. Neurobiological mechanisms for opponent motivational processes in addiction. Philos. Trans. R. Soc. London. B Biol. Sci. 363, 3113–3123. doi: 10.1098/rstb.2008.0094
Kosten, T. A., Miserendino, M. J., Chi, S., and Nestler, E. J. (1994). Fischer and Lewis rat strains show differential cocaine effects in conditioned place preference and behavioral sensitization but not in locomotor activity or conditioned taste aversion. J. Pharmacol. Exp. O iina. 269, 137-144.
Kosten, T. A., Zhang, X. Y., and Haile, C. N. (2007). Strain differences in maintenance of cocaine self-administration and their relationship to novelty activity responses. Faʻatasi. Neurosci. 121, 380-388. Pule: 10.1037 / 0735-7044.121.2.380
Leeman, RF, ma Potenza, MN (2012). Tulaga tutusa ma eseesega i le va o taaloga faitupe faʻamaʻi ma faʻafitauli o le faʻaaogaina o vailaʻau: o le taulaʻi atu i le impulsivity ma le faʻamalosi. Psychopharmacology (Berl.) 219, 469–490. doi: 10.1007/s00213-011-2550-7
Leshner, A. I. (1997). Addiction is a brain disease, and it matters. saienisi 278, 45â € "47. doi: 10.1126 / science.278.5335.45
Loba, P., Stewart, S. H., Klein, R. M., and Blackburn, J. R. (2001). Manipulations of the features of standard video lottery terminal (VLT) games: effects in pathological and non-pathological gamblers. J. Gambl. Stud. 17, 297–320. doi: 10.1023/A:1013639729908
Martinez, D., Narendran, R., Foltin, R. W., Slifstein, M., Hwang, D. R., Broft, A., et al. (2007). Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am. J. Fomaʻi 164, 622-629. doi: 10.1176 / appi.ajp.164.4.622
Mateo, Y., Lack, C. M., Morgan, D., Roberts, D. C., and Jones, S. R. (2005). Reduced dopamine terminal function and insensitivity to cocaine following cocaine binge self-administration and deprivation. Neuropsychopharmacology 30, 1455-1463. doi: 10.1038 / sj.npp.1300687
Nestler, EJ (2001). Fa'avae mole o le palasitika umi o lo'o fa'avae vaisu. Nat. Rev. Neurosci. 2, 119-128. Pule: 10.1038 / 35053570
Nieuwenhuis, S., Heslenfeld, D. J., von Geusau, N. J., Mars, R. B., Holroyd, C. B., and Yeung, N. (2005). Activity in human reward-sensitive brain areas is strongly context dependent. Neuroimage 25, 1302-1309. doi: 10.1016 / j.neuroimage.2004.12.043
Pierce, R. C., and Kalivas, P. W. (1997). A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res. Brain Res. Faaa. 25, 192. doi: 10.1016/S0165-0173(97)00021-0
Robbins, T. W., and Everitt, B. J. (1999). Drug addiction: bad habits add up. natura 398, 567-570. Pule: 10.1038 / 19208
Robinson, T. E., Becker, J. B., and Presty, S. K. (1982). Long-term facilitation of amphetamine-induced rotational behavior and striatal dopamine release produced by a single exposure to amphetamine: sex differences. Brain Res. 253, 231–241. doi: 10.1016/0006-8993(82)90690-4
Robinson, TE, ma Berridge, KC (1993). O le faavae faʻavae o fualaau oona: o se faʻaosofiaga-faʻalauiloa manatu o vaisu. Brain Res. Brain Res. Faaa. 18, 247–291. doi: 10.1016/0165-0173(93)90013-P
Robinson, TE, ma Berridge, KC (2001). Siʻitia-faʻapitoa ma le tagofia o vaisu. onāga i vailāʻau 96, 103-114. Pule: 10.1046 / j.1360-0443.2001.9611038.x
Singer, B. F., Scott-Railton, J., and Vezina, P. (2012). Unpredictable saccharin reinforcement enhances locomotor responding to amphetamine. Faʻatasi. Brain Res. 226, 340-344. Pule: 10.1016 / j.bbr.2011.09.003
Singh, V., and Khan, A. (2012). Decision making in the reward and punishment variants of the iowa gambling task: evidence of “foresight” or “framing”? I luma. Neurosci. 6: 107. Pule: 10.3389 / fnins.2012.00107
Skinner, B. F. (1953). Saienisi ma amioga a le tagata. New York, NY: Free Press.
Smart, K., Desmond, R. C., Poulos, C. X., and Zack, M. (2013). Modafinil increases reward salience in a slot machine game in low and high impulsivity pathological gamblers. Neuropharmacology 73, 66-74. Tui: 10.1016 / j.neuropharm.2013.05.015
Tremblay, A. M., Desmond, R. C., Poulos, C. X., and Zack, M. (2011). Haloperidol modifies instrumental aspects of slot machine gambling in pathological gamblers and healthy controls. Faʻaaoga. Biol. 16, 467-484. Pule: 10.1111 / j.1369-1600.2010.00208.x
Vanderschuren, L. J., and Kalivas, P. W. (2000). Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl.) 151, 99-120. Pule: 10.1007 / s002130000493
Vanderschuren, L. J., and Pierce, R. C. (2010). Sensitization processes in drug addiction. Curr. Top. Behav. Neurosci. 3, 179–195. doi: 10.1007/7854_2009_21
Vanderschuren, L. J., Schoffelmeer, A. N., Mulder, A. H., and De Vries, T. J. (1999). Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine. Psychopharmacology (Berl.) 143, 244-253. Pule: 10.1007 / s002130050943
Verdejo-Garcia, A., Lawrence, A. J., and Clark, L. (2008). Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies. Neurosci. Biobehav. Faaa. 32, 777-810. doi: 10.1016 / j.neubiorev.2007.11.003
Vezina, P. (2004). Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci. Biobehav. Faaa. 27, 827-839. doi: 10.1016 / j.neubiorev.2003.11.001
Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Gatley, S. J., Hitzemann, R., et al. (1997). Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. natura 386, 830-833. doi: 10.1038 / 386830A0
Volkow, ND, Wang, GJ, Fowler, JS, ma Tomasi, D. (2012). Lisi o vaisu i le fai'ai o le tagata. Annu. Rev. Pharmacol. Toxicol. 52, 321–336. doi: 10.1146/annurev-pharmtox-010611-134625
Winer, B. (ed.). (1971). Statistical Principles in Experimental Design. New York, NY: McGraw-Hill.
Zack, M., and Poulos, C. X. (2004). Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers. Neuropsychopharmacology 29, 195-207. doi: 10.1038 / sj.npp.1300333
Zack, M., and Poulos, CX (2009). Tulaga tutusa mo le dopamine i taaloga faitupe ma vaisu psychostimulant. Curr. Fa’aaoga fualaau faasaina Rev. 2, 11-25. Pule: 10.2174 / 1874473710902010011
Zamudio, S., Fregoso, T., Miranda, A., De La Cruz, F., and Flores, G. (2005). Strain differences of dopamine receptor levels and dopamine related behaviors in rats. Brain Res. Bull. 65, 339–347. doi: 10.1016/j.brainresbull.2005.01.009
Keywords: pathological gambling, sensitization, amphetamine, dopamine, uncertainty
Citation: Zack M, Featherstone RE, Mathewson S and Fletcher PJ (2014) Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine in rats. I luma. Faʻatasi. Neurosci. 8: 36. doi: 10.3389 / fnbeh.2014.00036
Na maua: 01 Novema 2013; Talia: 23 Ianuari 2014;
Published online: 11 February 2014.
Faatonutonu e:
Bryan F. Singer, Iunivesite o Michigan, ISA
Toe iloiloina e:
Louk Vanderschuren, University of Utrecht, Netherlands
Ruud Van Den Bos, Radboud University Nijmegen, Netherlands
Patrick Anselme, University of Liège, Peleseuma
Copyright © 2014 Zack, Featherstone, Mathewson and Fletcher. This is an open-access article distributed under the terms of the Laisene Creative Commons (CC BY). O le faʻaaogaina, tufatufa poʻo le toe gaosia i isi fonotaga e faatagaina, pe'ā tuʻuina atu le uluaʻi tusitala poʻo le laiseneina ma o le uluaʻi lomiga i totonu o lenei tusi o tala o loʻo taʻua, e tusa ai ma aʻoaʻoga faʻapitoa taliaina. Leai se faʻaaogaina, tufatufa poʻo le toe gaosia e faʻatagaina lea e le tausisia nei tuutuuga.
*Correspondence: Martin Zack, Cognitive Psychopharmacology Laboratory, Neuroscience Department, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada e-mail: [imeli puipuia]
;