Boiketlo ba ho kopanela liphate ka c-Fos ho Nucleus Accumbens le mosebetsi oa Amphotamine-Stimulated Locomotor Se Sensitized ke Phihlelo ea Pele ea Likamano Tsa Botona le Botšehali ka Hamsters ea Basyria ea Basyria (2001)

Journal of Neuroscience, 15 March 2001, 21(6): 2123-2130;

  1. Katherine C. Bradley1 'me
  2. Robert L. Meisel2

+ Boikarabello ba Mongoli


  1. 1 Lenaneo la Neuroscience la Grato,

  2. 2 Lefapha la Saense ea Psychological, Univesithi ea Purdue, West Lafayette, Indiana 47907-1364

inahaneloang

Ho fetisoa ha dopamine ka har'a li-bokellase tsa nucleus ho ka butsoa ka lithethefatsi, khatello ea maikutlo, kapa boits'oaro bo khothalletsoang, 'me ho pepesehela maikutlo ana khafetsa ho ka utloisa karabelo ena ea dopamine. Morero oa thuto ena e ne e le ho bona hore na boitšoaro ba basali ba ts'ebetso ea thobalano bo kenya li-neuron le hore na boiphihlelo ba nako e fetileng ba thobalano bo lemoha likarabo tsa neuronal ka har'a li-nucleus tsa li-amphtamine. U sebelisa mochine oa khatiso ea immunocytochemical, polelo ea c-Fos maemong a fapaneng (khetla ea khetla karolong ea rostral, e bohareng le ea boemo ba "patus" ea li-nucleus e ile ea hlahlojoa ho li-hamsters tsa basali tse neng li e-na le liphihlelo tse fapaneng tsa bootsoa. Li-hamsters tsa basali, tse fuoang libeke tsa 6 tsa bootsoa kapa tse setseng tsa bootsoa, ​​li ile tsa lekoa bakeng sa boitšoaro ba thobalano ka ho pepesetsoa li-hamsters tsa banna ba baholo. Boiphihlelo ba pele ba thobalano bo eketsehile c-Fos ho ngola maemong a rostral le a caudal empa eseng maemong a mahareng a li-nucleus accumbens. Teko ea boitšoaro ba thobalano e ile ea eketsa ho ngolla holimo, empa eseng khetla, ea li-nucleus bokellaneng. Ho netefatsa hore boitšoaro ba basali ba thobalano bo ka utloisa li-neurons tseleng ea mesolimbic dopamine, likarabo tsa locomotor tsa basali ba nang le boiphihlelo ba botona le botšehali ka ente ea amphetamine li ile tsa bapisoa. Amphetamine e ile ea eketsa tšebetso e akaretsang ea locomotor ho basali bohle. Leha ho le joalo, liphoofolo tse nang le tsebo ea thobalano li ile tsa arabela kapele ho amphetamine ho feta liphoofolo tse tenang ka thobalano. Lintlha tsena li bonts'a hore boitšoaro ba basali ba thobalano bo ka kenya tšebetsong li-neuron ka har'a li-nucleus tse bokellaneng le hore boiphihlelo ba thobalano bo ka tsibosa likarabo tsa neuronal ho amphetamine. Ntle le moo, liphetho tsena li fana ka bopaki bo eketsehileng ba liphapang tse sebetsang pakeng tsa khetla le bohare ba li-nucleus bokellase le mahlakore a eona a anteroposterior.

Li-neuron tsa dopamine tse hlahang sebakeng sa subbrain ventral tegmental le ho hlahisa li-nucleb tse fapaneng tsa forebrain, ho kenyelletsa le li-nucleus accumbens, ke karolo ea tsamaiso ea mesolimbic dopamine. Ho fanoe ka tlhahiso ea hore mokhoa ona oa dopamine o bohlokoa bakeng sa taolo ea boits'oaro ba takatso ea lijo (Mitchell le Gratton, 1994; Salamone, 1994, 1996; Ikemoto le Panksepp, 1999), le mokhoa oa ho itlhompha oa lithethefatsi tsa tlhekefetso (Pierre le Vezina, 1998;Koob, 1999; Lorrain et al., 1999; McKinzie et al., 1999; Batho et al., 1999; Bradberry et al., 2000). Tsamaiso ea systemic ea lithethefatsi tse fapaneng tsa tlhekefetso (mohlala, cocaine, amphetamine, le heroin) e kenya ts'ebetsong dopamine pathways (Pontieri et al., 1995; Nisell et al., 1997; Pierce le Kalivas, 1997a; Tanda et al., 1997; Tanda le Di Chiara, 1998; Barrot et al., 1999; Cadoni le Di Chiara, 1999), le ho pepesetsoa khafetsa litsing tsena tsa meriana ho ka utloisa li-neuron tsena tse arabelang ka dopamine (Robinson et al., 1988; Kalivas le al., 1992; Kalivas le Duffy, 1993; Pierce le Kalivas, 1995; Kuczenski et al., 1997; Nisell et al., 1997; Birrell le Balfour, 1998; Heidbreder le Feldon, 1998; Cadoni le Di Chiara, 1999; Cadoni et al., 2000). Patlisiso e fane ka bopaki ba hore li-nucleus li bokellana le tsona li arabela ho thepa e itseng e amanang le ho ruruha. Maemo a dopamine ea extracellular ho "nucleus" a bokellanang a eketseha nakong ea likamano tsa botona le botšehali ho likhoto tsa basali (Mermelstein le Becker, 1995; Pfaus et al., 1995) le hamsters (Meisel et al., 1993; Kohlert et al., 1997; Kohlert le Meisel, 1999). Hoa tšoana le khafetsa taolo ea lithethefatsi, liteko tse ngata tsa thobalano le tsona li eketsa nyollo ea methapo ea dopamine, e fana ka maikutlo a hore boiphihlelo ba thobalano bo ka nolofatsa methapo ea kutlo tseleng ea dopamine (Kohlert le Meisel, 1999).

Li-nucleus accumbens li entsoe ka likarolo tse ngata tse ikhethang tse ikhethileng, tseo hangata e leng khetla le konokono. Likamano tse mabapi le khetla le khetla ea mantlha li fana ka maikutlo a hore likhakanyo tsena tse peli li laola mesebetsi e fapaneng.Crawley et al., 1985a,b; Heimer et al., 1991; Zahm le Brog, 1992; Brog et al., 1993;Kalivas le Duffy, 1995; Maldonado-Irizarry et al., 1995; Pierce le Kalivas, 1995; Pontieri et al., 1995; Broening et al., 1997; Heimer et al., 1997; Kelley et al., 1997; Stratford le Kelley, 1997; Heidbreder le Feldon, 1998; Lanca et al., 1998; Bassareo le Di Chiara, 1999; Di Chiara et al., 1999b; Groenewegen et al., 1999; Kelley, 1999; McKinzie et al., 1999; Zahm, 1999; Brown le Molliver, 2000). Hobane li-nucleus accumbens ke ntho e tsoetseng pele, ha ho hlake hore na likarabelo tsa boitšoaro ba basali ba thobalano li fumaneha sebakeng se itseng sa subusters tsa li-nucleus kapa li hasantsoe ho potoloha leqhubu lohle. Mahlale a neng a kile a sebelisoa ho araba potso ena (mohlala, maqhubu a Microbalalization) ha a na kutloelo-pele ea tlhaho ho lekola ts'ebetso ea heterogeneity ea li-accumbens. Ho fapana le moo, ts'ebetso ea immunocytochemical ea protheine ea c-Fos e fana ka mokhoa oa ho hlahloba ho kenella ha selefouno har'a likarolo tse tlase tsa li-nucleus accumbens. Kahoo, sepheo sa pele sa teko ena e ne e le ho bona hore na ts'ebetso ea selula ka mora ts'ebetso ea thobalano ea basali e fumaneha libakeng tse ikhethileng tsa li-nucleus tse bokellaneng.

Thepa e khahlisang ea litsela tsena tsa dopamine ke maikutlo a sefapano. Ka mantsoe a mang, li-neurop tsa dopamine tseo pele li neng li khothalelitsoe ho setheo se le seng li tla bonts'a likarabo tse angoeng ke moriana o mong o fuoeng lekhetlo la pele (Cunningham le Kelley, 1992; Pierce le Kalivas, 1997a; Birrell le Balfour, 1998; Taylor le Horger, 1999). Ntle le tšusumetso ea maikutlo lipakeng tsa lithethefatsi, liphuputso tse 'maloa li tlalehile tšitiso pakeng tsa ho pepesetsoa khafetsa ho li-pharmacological agents le boits'oaro bo susumetsang ba tlhaho (Mitchell le Stewart, 1990a,b; Tidey le Miczek, 1997; Fiorino le Phillips, 1999). Ka hona, re ile ra hlahloba hore na liphoofolo tse nang le tsebo ea thobalano le tsa thobalano li ka arabela ka mokhoa o fapaneng ts'usumetsong ea lipale e tsejoang ho kenya ts'ebetsong dopamine pathways (ke hore, maikutlo a sefapano), joalo ka amphetamine. Haeba boitšoaro ba basali ba thobalano bo khotsofatsa litseleng tsa dopamine, basali ba nang le thobalano ba lokela ho fana ka karabelo e ntlafalitsoeng ea boitšoaro ka ente e le 'ngoe ea amphetamine.

LISEBELISOA LE MEKHOA

Mekhoa e akaretsang

Liphoofolo. Li-hamsters tsa banna le basali tsa Basyria li lopolotsoe ho Charles River Laboratories (Kingston, NY) ka ∼60 d ea lilemo. Tse tšehali li ne li bolokoa ka bonngoe, 'me liphoofolo tse matlafatsang tsa banna li ne li beoa ka lihlopha tsa ba bararo kapa ba bane ka mekotla ea polasetiki (50.8 × 40.6 × 20.3 cm). Kamore ea kolone ea liphoofolo e hlokometsoe mocheso o sa feleng (22 ° C) 'me mabone a tima pakeng tsa 1: 30 le 11: 30 PM (14 / 10 hr leseli / potoloho e lefifi). Lijo le metsi li ne li fumaneha ad libitum.

Mekhoa e sebelisitsoeng boitekong bona e ipapisitse le Institutes tsa Bophelo ba Naha Litaelo tsa tlhokomelo le tšebeliso ea liphoofolo tsa liphoofolo mme ba amohetswe ke Komiti ea Tlhokomelo ea Liphoofolo le Ts'ebeliso ea Purdue.

Boiphihlelo ba thobalano. Hoo e ka bang beke ea 1 kamora hore basali ba fihle laboratoring, ba ile ba emeloa ka mahlakore a mabeli ka tlasa sodium pentobarbital (Nembutal) anesthesia (8.5 mg ka boima ba 'mele oa 100 gm, ip). Kamora ho ovariectomy, qalong basali ba ile ba aroloa ka lihlopha tse peli. Sehlopha se le seng sa basali se fumane libeke tsa 6 tsa boiphihlelo ba botona le botšehali; sehlopha sa bobeli se ile sa lula se se na tsebo. Basali bohle ba ne ba holisoa ka nako e le 'ngoe ka beke bakeng sa nako ea beke ea 6. Ka bobeli ba 48 le 24 hr pele ho boiphihlelo ba botona le botšehali, tse tšehali li ile tsa kenngoa ka mokhoa o sa ts'oaneng ka 10 μg ea estradiol benzoate ho 0.1 ml ea oli ea cottonseed. Ka letsatsi la tlhahlobo ea boiphihlelo, basali ba ile ba fumana 500 μg ea progesterone ho 0.1 ml ea oli ea cottonseed (subcutaneous sindano). Basali ba sa fumanang boiphihlelo ba botona le botšehali ba ne ba kenngoa ka mofuta oa li-hormone mme ba lula malapeng a bona ka phapusing ea kolone. Ho 4-5 hr kamora ts'ebetso ea progesterone, monna e moholo oa monna ea neng a nkile boiphihlelo ka thobalano ka ts'ebeliso lithutong tse ling tsa boits'oaro ba thobalano o ile a beoa kahara ntlo ea mosali ea liteko. Taelo ea likhotla tse tšehali e ne e potoloha beke e 'ngoe le e' ngoe ho fokotsa menyetla ea hore monna le mosali ba raloa ka makhetlo a fetang le le leng nakong ea libeke tsa 6 tsa bootsoa.

Immunocytochemistry. Li-hamsters tsa basali, tse bolailoeng ka overdose ea sodium pentobarbital, li ile tsa tlotsoa ka botebo ka 25 mm Tharollo ea PBS, pH 7.5, bakeng sa 2 min (sekhahla sa phallo, 25 ml / min), e lateloe ke 4% paraformaldehyde ho PBS bakeng sa 20 min. Li-brine li ne li kentsoe ka morao bakeng sa 2 hr ho paraformaldehyde mme li bolokiloe ka 10% sucrose PBS bosiu bo le bong ho 4 ° C.

Likarolo tsa serame tsa 40 μm tsa serame li ile tsa nkuoa ka mahlakore 'ohle a li-nucleus. Kamora ho hlaseloa ka makhetlo a mararo a 10 min ho PBS, likarolo li ile tsa kenngoa ho antibody ea mantlha ho c-Fos (1: 6000 ho PBS e nang le 0.3% Triton X-100; Santa Cruz Biotechnology, Santa Cruz, CA) kapa ka antibody ea mantlha ho calbindin-D (28 kDa) (1: 6000 ho PBS e nang le 0.3% Triton X-100; Chemicon International, Temecula, CA) ho 4 ° C bakeng sa 48 hr. Likarolo ka bobeli tsa c-Fos le calbindin-D li ile tsa kenngoa mocheso oa kamore ea 45 ka kamoreng ea mocheso oa biotinylated anti-rabi IgG bobeli antibody (1: 200 in PBS; Elite Vectastain ABC kit; Vector Laboratories, Burlingame, CA), ea lateloa ke an incubation e nang le avidin-biotin horseradish peroxidase (1: 50 in PBS; Elite Vectastain ABC kit) bakeng sa 45 min mocheso oa kamoreng, ka li-rinses tse tharo tsa 10 min ho PBS pele ho ho kenella ka nako e ngoe le e ngoe. Kamora ho rinses tse peli ho PBS le rinse ea 10 min ho 0.1 m Tris buffer, pH 7.6, likarolo tsa c-Fos le calbindin-D li ne li entsoe bakeng sa 5 le 10 min, ka ho latellana, ho 0.08% diaminobenzidine (DAB) (Aldrich, Milwaukee, WI) ho Tris buffer e nang le 0.003% hydrogen peroxide le 0.015% chloride ea nickel. Likarolo tsohle li ile tsa ts'oaroa hape ka Tris buffer le metsi a deion mme li beoa holim'a li-slide tsa chrom-alum. Li-slide li ile tsa omisoa, tsa haelloa ke metsi, tsa hlakisoa, 'me tsa koaheloa ka tšebeliso li sebelisa Permount (Fisher Science science, Pittsburgh, PA).

Tlhahlobo ea microscopic. Nama ea Neural e etselitsoeng calbindin-D, e khethollang khetla le konokono ea li-nucleus tse bokellaneng (Jongen-Relo et al., 1994a; Johnson le Wood, 1999) e ne e sebelisoa ho supa karolo e ngoe le e ngoe maemong a rostral, bohareng, le caudal ea dorsal nucleus accumbens. Likarolo tse tsoang bokong ba liqhubu sebakeng sa rostral, bohareng le tsa caudal tse bonts'itsoeng ka calbindin li bontsitsoe ho Setšoantšo. 1 A-C. Ho tlalehiloe hore ho na le phapang e fokolang pakeng tsa mantlha le khetla ho ts'oaetso ea calbindin-D ho Hamster ea Syria ha e bapisoa le rat, empa ho ts'oara peptide ena ho ntse ho khona ho khetholla likarolo tse ka tlase tsa li-nucleus accumbens (Johnson le Wood, 1999). Lebokose le akaretsang sebaka sa sampole sa 0.1 mm2 (0.2 × 0.5 mm) e ile ea beoa ka holim'a khetla ea dorsal le konokono ea li-nucleus tse bokelletsoeng bakeng sa karolo ka 'ngoe. Setšoantšo sa karolo ka 'ngoe se ne se hatisoa filiming e sa bonahaleng' me litšoantšo li ne li ts'oaroa likarolo tse tsamaellanang le tsa C-Fos bakeng sa phoofolo ka 'ngoe, ho etsa bonnete ba hore liphoofolo tsohle li behiloe ka har'a lekhetho. Setšoantšo 1, D 'me E, e bontša karolo e le 'ngoe ea caudal ho phoofolo e amohetseng libeke tsa 6 tsa boiphihlelo ba thobalano mme e ile ea lekoa bakeng sa boitšoaro ba thobalano. Lebokose le ile la beoa karolong e kaholimo ea li-bokellase tsa caudal ho Setšoantšo 1 Dle khetla ea lintho tse bokellaneng ka har'a tsona1 E. Lebokose le nang le litekanyo tse tšoanang le ne le behiloe karolong e le 'ngoe ea lisele ka har'a cingate cortex e bohareng le kaholimo ho mokokotlo oa mahareng le o ka morao oa dorsal caudate ho e' ngoe le e 'ngoe ea litekanyetso tse tharo tse sampetsoeng bakeng sa li-nucleus accumbens. Hobane re nahanne hore ho ka ba le phapang ea rostral – caudal liphellong tsa ho nyalana ha c-Fos, ke karolo e le 'ngoe feela boemong ka bong e ileng ea hlahlojoa ho eketsa tatellano ea anatomical ea sampling ea rona. Palo ea lisele tsa c-Fos-immunoreactive sebakeng se seng le se seng se khethiloeng li ile tsa baloa ka thuso ea k'hamera ea video e hokahantsoeng le sistimi ea tlhahlobo ea litšoantšo ea k'homphieutha (BioQuant MegM; R & M Biometrics, Nashville, TN).

Setšoantšo sa 1.

Likarolo tsa litho tsa nyutlelie li bokelletsoeng calbindin-D le c-Fos. A-C ke likarolo tse tsoang rostral (A), bohareng (B), le caudal (C) li-nucleus accumbens tse lenngoeng (bohareng ke letšehali) bakeng sa calbindin, e bontšang karohano lipakeng tsa khetla le subregions tsa mantlha (asterisks). Ho na le 320 μm pakeng tsa likarolo tsa rostral le tse bohareng le 240 μm lipakeng tsa likarolo tse lipakeng le tsa caudal. Litšoantšo tse ka tlase (D, E) ke mehlala ea li-c-Fos tse hlahelletseng ho mantlha ea caudal (D) le shell (E) ea li-nucleus accumbens (bohareng ke tokelo) ea mosali ea nang le thobalano ea bolailoeng kamora tlhahlobo ea boitšoaro ba thobalano. Thekhutlonne e bontša sebaka sa sampling (0.2 × 0.5 mm).

Teko ea 1

Teko ea pele e ile ea etsa lipatlisiso ka litlamorao tsa boiphihlelo ba thobalano le liteko tsa ho kenella ka c-Fos bokong ba li-nucleus, le dorsal caudate nucleus le cingex cortex. Morero oa teko ena o ne o habeli. Morero oa pele e ne e le ho bona hore na ho na le phapang ea ts'ebetso ea selefouno ho a mang a libaka tsa boko ka lebaka la boiphihlelo ba pejana ba thobalano le / kapa tlhahlobo ea boitšoaro. Haeba polelo ea c-Fos e ne e fetotsoe, ho ne ho tla khethoa hore na liphetoho li ka fetisoa libakeng tse ikhethileng kahare ho likarolo tse tharo tsa kelello tse hlahlobiloeng.

Li-hamsters tsa basali tsa Basyria li fumane libeke tsa 6 tsa bootsoa kapa tsa lula li le boi. Nakong ea libeke tsa 6 tsa boiphihlelo, nako e eketsehang eo mosali a neng a nahana hore ke Lordosis (ho se tsamaisane le ts'ebetso ea dorsoflexion ea morao) e neng e lekantsoe bakeng sa kemiso e ngoe le e ngoe ea 10 min. Ha ho na mehato ea boitšoaro ba banna e tlalehiloeng. Bekeng ea 7, ho ile ha fanoa ka letoto le tšoanang la li-entradiol benzoate le progesterone. Lekhetlong lena, halofo ea basali ba nang le boiphihlelo le ba se nang bohlola ba ile ba lekoa bakeng sa boitšoaro ba thobalano ka ho beha e motona e moholo khoeleng ea bona ea lapeng. Tse tšehali tse setseng li ile tsa siuoa ka har'a matloana a tsona. Motseng oa 60-90 kamora ho pepesehela e tona, tse tšehali li ile tsa etsoa ka mokhoa o hlakileng, 'me likelello tsa tsona tsa sebetsoa bakeng sa polelo ea c-Fos. Basali bao ba sa kang ba hlahlojoa bakeng sa boitšoaro ba thobalano ba ile ba ferekanngoa le 4 hr kamora tsamaiso ea progesterone

Tlhahlobo ea lintlha. Hobane lipalo tsa sele li ne li sa fapana lipakeng tsa basali bao ba sa hlahlobeloang boitšoaro ba thobalano nakong ea beke ea 7, ho sa tsotelehe boiphihlelo ba thobalano bo fetileng (bona Lethathamo1 mohlala), basali ba liteko ba ile ba qetella ba arotsoe ka lihlopha tse tharo tsa kalafo bakeng sa tlhahlobo. Sehlopha sa pele se ne se e-na le basali ba fumaneng libeke tsa 6 tsa bootsoa mme ba lekoa bakeng sa boitšoaro ba thobalano (boiphihlelo / tlhahlobo, n = 6). Sehlopha sa bobeli se ne se e-na le basali bao ba sa kang ba fumana boiphihlelo bo fetileng, empa ba ile ba lekoa bakeng sa boitšoaro ba thobalano (ha ba na boiphihlelo / tlhahlobo,n = 8). Sehlopha sa ho qetela se ne se na le li-hamsters tsohle tse sa kang tsa hlahlojoa hore na li etsa thobalano joang, ho sa tsotelehe boiphihlelo bo fetileng ba thobalano (ha ho na liteko, n = 13). Lihlopha tsena tse peli tse sa fumaneng tlhahlobo ea boitšoaro ba thobalano li ne li kopantsoe ho eketsa matla a lipalo tlhahlobisong. Palo ea lisele tse emeng ka c-Fos tse tsoang li-dorsal nucleus bokellase, dorsal caudate nucleus, le cingex cortex li ile tsa bapisoa har'a lihlopha tsena tse tharo.

Tafole 1.

Ho bapisoa le ho bolela ± SEM palo ea lisele tsa c-Fos-immunoreactive tse bokong li bokellana khubung le bohareng lipakeng tsa lihlopha tsa kalafo ea liteko.

Lipalo tsa lisele li ile tsa hlahlojoa ho sebelisoa li-multifactor ANOVA. Li-ANOVA tse bonolo tsa sephetho le post hoc Liteko tsa Newman-Keuls li entsoe moo ho loketseng. Lintlha tsa Boitšoaro (Lord durations) li ile tsa hlahlojoa ho sebelisoa mehala e 'meli t teko.

Teko ea 2

Teko ea bobeli e ile ea bapisa bokhoni ba tšusumetso ea nalane, amphetamine, ho hlahisa maikutlo a boits'oaro ho basali ba nang le boits'oaro ba botona le botšehali ba sa nyalanang. Polelo ea c-Fos ho li-nucleus accumbens, dorsal caudate nucleus, le cingex cortex e ile ea hlahlojoa hape ho bona hore na sebopeho sa mesebetsi ea mahlale se ts'oana le sephetho se fumanoeng ho Thutong ea 1.

Li-hamsters tsa basali tsa Basyria li ile tsa fuoa libeke tsa 6 tsa boiphihlelo ba thobalano kapa tsa lula li se na tsebo. Bekeng ea 7, basali bohle ba ne ba isoa tikolohong ea lipale (ka ho re, 10 gallon galone aquarium ka phapusing e sa tsejoeng) 4 hr kamora tsamaiso ea progesterone. Tse tšehali li ile tsa beoa kahara metsi a khalase ea galase ea 10 bakeng sa 10 min, kamora nako eo halofo ea basali ba nang le thobalano e nang le thobalano le batho ba hlokang thobalano e ne e beoa.d-amphetamine sulfate (1 mg ka boima ba 'mele ba 1 kg ho 1.0 ml ea 0.9% NaCl; mpho e tsoang ho Dr. David Nichols, Univesithi ea Purdue). Basali ba setseng ba ne ba kenngoa ka 0.9% NaCl (1 mg ka boima ba 'mele oa 1 kg). Tse tšehali li ile tsa khutlisetsoa ka har'a 10 gallon aquarium bakeng sa 60 min e eketsehileng. Mananeo a 70 a metsotso a ile a vouta ho hlahlojoa ha tšebetso ea kakaretso ea basali. Ka hare ho metsotso ea 30 kamora tlhahlobo e akaretsang ea tšebetso, basali ba entsoe ka mokhoa o hlakileng, 'me likelello tsa bona li ile tsa sebetsoa bakeng sa polelo ea c-Fos.

Tlhahlobo ea Videotape. Bekeng ea 7, mananeo a 70 a neng a ntse a lekoa ka sepheo sa litaba a fumaneha ka videot. Li-aquariums tsa khalase tsa khalase tsa 10 li ile tsa aroloa likarolo tse tharo tse lekanang skrineng sa video, 'me tšebetso ea li-locomotor ea basali e tlalehiloe ho latela palo ea lifapano tsa sebaka.

Tlhahlobo ea lintlha. Nalane ea nakong e fetileng ea thobalano ha e a ka ea susumetsa tšebetso ea li-hamsters tsa basali tse kentsoeng letsoai; ka hona, basali ba liteko ba arotsoe ka lihlopha tse tharo tsa kalafo bakeng sa ho hlahlojoa. Sehlopha sa pele se ne se na le basali ba fumaneng libeke tsa 6 tsa bootsoa mme ba kenngoa le amphetamine (boiphihlelo / amphetamine, n = 8). Sehlopha sa bobeli se ne se e-na le basali bao ba neng ba fuoa amphetamine empa ba sa fumane boiphihlelo ba bootsoa (ha ba na boiphihlelo / amphetamine,n = 8). Sehlopha sa ho qetela se ne se na le li-hamsters tsohle tse tšetsoeng ka letsoai, ho sa tsotelehe boiphihlelo bo bong ba pele ba thobalano (saline, n = 15). Ts'ebetso ea mofuta oa feminotor ea basali e bapisoa le lihlopha tse tharo tsa kalafo ho pholletsa le liteko tsa 70 tsa liteko (ka linako tsa metsotso ea 10) li sebelisa li-ANOVA tse peli. Li-ANOVA tse bonolo tsa sephetho le post hoc Liteko tsa Newman-Keuls li entsoe moo ho loketseng.

Palo ea lisele tse khethiloeng bakeng sa c-Fos e ne e sa fapana lipakeng tsa basali bao ka ente ea letsoai, ho sa tsotelehe boiphihlelo ba pele ba thobalano. Ka hona, lipalo tsa lisele tse nang le c-Fos tse tsoang li-dorsal nucleus kukusanya, dorsal caudate nucleus, le cingex cortex li ile tsa bapisoa har'a lihlopha tse tharo tse tšoanang tsa kalafo joalo ka ha ho etsoa liteko tsa pele. Lipalo tsa lisele li ile tsa hlahlojoa ho sebelisoa li-multifactor ANOVA. Li-ANOVA tse bonolo tsa sephetho le post hoc Liteko tsa Newman-Keuls li entsoe moo ho loketseng.

LIPOTSO

Teko ea 1

Mehato ea boitšoaro ba thobalano

Nako ea Lordosis nakong ea liteko tsa boitšoaro ba thobalano bekeng ea 7 e ne e bapisoa pakeng tsa boiphihlelo / tlhahlobo le lihlopha tse se nang boiphihlelo / tsa liteko. Nako e tloaelehileng ea Lordosis nakong ea liteko tsa 10 min e ne e le 341 ± 53 sec bakeng sa boiphihlelo / sehlopha sa liteko le 478 ± 20 sec bakeng sa sehlopha se se nang boiphihlelo / sa liteko. Basali ba se nang boiphihlelo / sehlopha sa tlhahlobo ba kile ba nahana hore ke Lordososis ka nako e telele haholo ho feta ho ba batšehali sehlopheng sa boiphihlelo / sehlopha sa liteko (t 6 = 5.131; p = 0.05). Ho feta moo, boiphihlelo ba thobalano ha bo a ama nako ea Lordosis. Tlhahlobo e bontšitse hore ha ho na phapang e kholo lipakeng tsa nako e telele ea beke ea 1 (399 ± 44 sec) le beke 7 (341 ± 53 sec) bakeng sa basali ba nang le boiphihlelo / sehlopha sa liteko.

polelo ea c-Fos ka har'a li-bokellase tsa nucleus

ANOVA ea mekhoa e meraro ea linako tsa kalafo rostral-caudal level times shell-msingi ha ea ka ea fumana litlamorao tsa kalafo mme ha ho na tšebelisano-mmoho pakeng tsa kalafo, boemo ba li-accumbens, le shell-core (sa feiga. 2); leha ho le joalo, ho ile ha fumanoa mekhoa e 'meli ea bohlokoa ea ho sebelisana (linako tsa kalafo nako ea mantlha ea kalafo le nako ea kalafo).

Setšoantšo sa 2.

polelo ea c-Fos khetla le bohare ba li-nucleus li bokellana maemong a rostral, bohareng le ba caudal bakeng sa sehlopha ka seng sa kalafo. ANOVA ea mekhoa e meraro (linako tsa kalafo rostral-caudal level times shell-core) e sebelisitsoe ho hlahloba litlamorao tsa boiphihlelo ba thobalano le boits'oaro ho se boleloang ke palo ea SEM ea lisele tsa c-Fos. Ha ho litlamorao tse kholo tsa kalafo ebile ha ho litšebelisano ka mekhoa e meraro lipakeng tsa kalafo, boemo ba li-accumbens, le motheo oa khetla e fumanoe.

Ho batla ha linako tsa kalafo ho sebelisana le ho ikatisa ho ile ha senola litlamorao tsa mantlha tsa lihlopha tsa kalafo feela karolong ea mantlha ea li-nucleus. 3). Papiso e ngata ea Pairwise e bonts'a hore basali bao ba ile ba lekoa bakeng sa boitšoaro ba thobalano nakong ea beke 7 (boiphihlelo / tlhahlobo 'me ha ba na boiphihlelo / tlhahlobo) ba ne ba e-na le lisele tse nang le c-Fos tse ka sehlohlolong sa li-nucleus tse bokellaneng ho feta tse tšehali tse sa kang tsa hlahlojoa. liteko) (Newman – Keuls, p <0.01). Ha ho na litlamorao tsa liteko tse bonoeng ka har'a khetla ea li-nucleus accumbens. Ntle le moo, ho ne ho se na litlamorao tse hlakileng tsa boiphihlelo ba thobalano palong ea lisele tse hlalosang c-Fos ka har'a khetla kapa khubung ea li-accumbens.

Setšoantšo sa 3.

polelo ea c-Fos khetla le bohare ba li-nucleus li oele, li ile tsa oela holima boemo ba "rostral-caudal". ANOVA ea mekhoa e meraro e senotse tšebelisano pakeng tsa mekhoa e 'meli lipakeng tsa kalafo mme e bolela number SEM palo ea lisele tsa c-Fos khetla le bohare ba li-nucleus accumbens (linako tsa kalafo tsa khetla-motheo;F (2,24) = 4.243; p<0.026). ANOVA ea tsela e le 'ngoe e lekolang ts'ebelisano ena e fumane litlamorao tse kholo tsa lihlopha tsa kalafo feela mokokotlong oa li-nucleus accumbens (F (2,24) = 7.341; p<0.003) eseng ka har'a khetla ea li-accumbens (F (2,24) = 1.271; p> 0.1). Litlhaku tse fapaneng bonts'a phapang e kholo lipakeng tsa lihlopha.

Mohlomong linako tsa kalafo tse sebelisanang le boemo ba kalafo ba rostral-caudal li fumane litlamorao tsa mantlha tsa lihlopha tsa kalafo maemong ohle a rostral le a caudal empa eseng maemong a mahareng a li-nucleus kukusanya. 4). Newman – Keuls post hoc Litlhahlobo li bonts'a hore basali ba neng ba amohetse libeke tsa 6 tsa bootsoa mme ba lekoa bakeng sa boitšoaro ba thobalano (boiphihlelo / tlhahlobo) ba ne ba e-na le lisele tse nang le c-Fos tse ngata ka har'a li-rostral nucleus accumbens ho feta tsa basali tse ileng tsa hlahlojoa empa tse sa kang tsa fumana boiphihlelo ba pejana ba thobalano (ha ho na boiphihlelo / tlhahlobo; p <0.05) le basali ba sa kang ba lekoa boits'oaro ba thobalano (ha ho teko;p <0.01). The post hoc Liteko li senotse sephetho se ts'oanang le tsa li-bokelle tsa caudal. Basali ba sehlopheng sa boiphihlelo / ba liteko ba ne ba e-na le lisele tse ngata tse hlalosang c-Fos ka har'a li-nucleus tsa caudal tse bokelloang ho feta tsa basali ba se nang boiphihlelo / sehlopha sa liteko (p <0.05) mme ha ho sehlopha sa liteko (p <0.01). Ka hona, ho lekoa boits'oaro ba thobalano bekeng ea 7 ho ne ho ekelitse palo ea lisele tse silafalitsoeng ke c-Fos mokokotlong oa li-rostral le caudal feela bakeng sa basali ba fumaneng libeke tsa 6 tsa boiphihlelo.

Setšoantšo sa 4.

polelo ea c-Fos ka sebopeho sa "rostral-caudal" ea "nucleus" e bokellaneng, e oele ka har'a motheo le khetla. Leha ANOVA e nang le mekhoa e meraro e bonts'itse hore tšebelisano-peli ea lipakeng tsa lihlopha tsa kalafo le se boleloang ke lisele tsa "CEM" tsa SEM palo ka li-rostral-caudal tsa li-nucleus tsa li-nucleus li atamelaneng feela ka bohlokoa ba tsona (F (4,48) = 2.365; p <0.066), re hlahlobile mohato o mong le o mong oa li-nucleus accumbens ka thoko bakeng sa kalafo ho c-Fos stain. ANOVA ea tsela e le 'ngoe e senotse litlamorao tse kholo tsa lihlopha tsa kalafo maemong a rostral (F (2,48) = 5.230; p<0.009) le boemo ba caudal (F (2,48) = 7.455; p <0.002) empa eseng maemong a bohareng (F (2,48) = 1.744; p> 0.1) ea li-nucleus accumbens. Litlhaku tse fapanengbonts'a phapang e kholo lipakeng tsa lihlopha.

polelo ea c-Fos mokokotlong oa caudate le cingrate cortex

Lipalo tsa sele ho tsoa moleng oa dorsal caudate le tsona li ile tsa hlahlojoa ho sebelisoa ANOVA ea mekhoa e meraro. Tlhahlobo e senotse tšebelisano lipakeng tsa kalafo le polelo ea c-Fos ho methapo ea kutlo le ea morao-rao ea caudate (F (2,24) = 3.514;p <0.046). Leha ho le joalo, tlhahlobo e arohaneng ea khubu e bohareng le e ka morao ka tsela e le 'ngoe ea ANOVA ha e bontše phapang palong ea lisele tse silafalitsoeng ke c-Fos lipakeng tsa boiphihlelo / teko, ha ho na boiphihlelo / teko ebile ha ho na lihlopha tsa liteko (Tafole2). Ntle le moo, ha ho litlamorao tse kholo tsa boiphihlelo ba thobalano kapa boits'oaro ho palo ea lisele tse hlalosang c-Fos, kapa tšebelisano efe kapa efe, li fumanoe cingex cortex (data e sa bonts'itsoeng).

Tafole 2.

Bolelang EM SEM palo ea lisele tsa c-Fos-immunoreactive methapong ea methapo le ea methapo ea methapo.

Teko ea 2

Ts'ebetso ea locomotor

ANOVA ea mekhoa e 'meli (nako ea tlhahlobo ea linako tsa kalafo), e bapisa ts'ebetso ea basali ka boiphihlelo / amphetamine, ha ho na boiphihlelo / amphetamine, le lihlopha tsa kalafo ea letsoai ho pholletsa le metsotso ea 70 ea tlhahlobo e bontšitse tšebelisano pakeng tsa sehlopha sa kalafo le nako ea tlhahlobo. Ho hlahloba tšebelisano ena, lihlopha tsa kalafo ka bomong li ile tsa botsoa ka thoko le li-ANOVA tsa tsela e le 'ngoe. Bohlahlobisisi bo bonts'itse liphetoho tse kholo molemong oa tšebetso e akaretsang nakong ea metsotso ea 70 ea liteko bakeng sa lihlopha tse peli tsa basali tse ileng tsa kenngoa ka amphetamine (boiphihlelo / amphetamine mme bo sena boiphihlelo / amphetamine). Leha ho le joalo, ts'ebetso e akaretsang ea basali e fumaneng saline ha ea ka ea fetoha haholo minong ea 70 (sa feiga.5). Newman – Keuls post hocLiteko li ile tsa sebelisoa ho fumana hore na linako tsa liteko tsa 10 tsa metsotso e ne e fapane le eng. Papiso e ngata ea Pairwise e bontšitse hore tšebetso e akaretsang ea basali ba nang le thobalano e fuoeng amphetamine e ile ea eketsa haholo 10 min kamora liente (p <0.05). Ntle le moo, ha e bapisoa le metsotso e 10 pele ho liente, basali ba nang le boiphihlelo / sehlopha sa kalafo sa amphetamine ba lula ba le mafolofolo haholo 20 min (p <0.05) le metsotso e 30 (p<0.05) kamora liente. Ka lehlakoreng le leng, litlamorao tsa amphetamine ho basali ba nang le thobalano li ne li sa bonahale ho fihlela 20 min kamora liente. Nakong ena, basali bana ba ne ba le mafolofolo haholo ha ba bapisoa le metsotso e 10 pele ho liente (p <0.05). Ntle le moo, tšebetso ea basali ba se nang botona le botšehali e fuoeng amphetamine e ile ea lula e eketsehile haholo bakeng sa 30 min (p <0.05) le metsotso e 40 (p<0.01) kamora liente.

Setšoantšo sa 5.

Litlamorao tsa amphetamine ketsahalong e akaretsang ea bo-hamsters ba basali ba nang le thobalano le ba sa kopaneleng thobalano. ANOVA ea mekhoa e 'meli (nako ea tlhahlobo ea linako tsa kalafo) e senotse tšebelisano pakeng tsa sehlopha sa kalafo le nako ea tlhahlobo (F (12,150) = 2.288;p <0.011) bakeng sa palo e bolelang ea ± SEM. ANOVA ea tsela e le 'ngoe e lekolang lihlopha tsa kalafo ka bomong e bonts'itse liphetoho tse kholo mesebetsing e akaretsang ea basali boiphihlelong / amphetamine (F (6,150) = 3.0468; p <0.008) mme ha ho na boiphihlelo / amphetamine (F (6,150) = 3.893;p <0.001) lihlopha tsa kalafo. Ts'ebetso ea basali ba kentsoeng letsoai ha ea fetohaF (6,150) = 1.619;p <0.1). Post hoc Liteko li bontšitse hore basali ba nang le thobalano ba arabile ka potlako ho amphetamine, ho bonts'a keketseho ea ts'ebetso ka hare ho min ea 10 ea pele kamora ho ente. Basali ba nang le tsebo ea botona le botšehali ha baa ka ba arabela amphetamine ho fihlela 20 min kamora ho ente. *p <0.05 khahlanong le nako ea pele ho liteko.

polelo ea c-Fos

ANOVA ea mekhoa e meraro (linako tsa kalafo rostral-caudal level times shell-core) e sebelisitsoe ho hlahloba litlamorao tsa boiphihlelo ba botona le botšehali le amphetamine polelong ea c-Fos ho li-nucleus accumbens. Ha ho litlamorao tse kholo tsa kalafo ebile ha ho litšebelisano ka mekhoa e meraro lipakeng tsa kalafo, boemo ba li-accumbens, le motheo oa khetla e fumanoe. Ntle le moo, tlhahlobo ha ea ka ea senola tšebelisano lipakeng tsa lihlopha tsa kalafo le polelo ea c-Fos ka har'a khetla le bohareng ba maqhubu kapa pakeng tsa lihlopha tsa kalafo le li-c-Fos tse ngotsoeng lipakeng tsa rostral, bohareng, le maemo a caudal a li-nucleus tse bokellaneng ( ya data ha e bontšoa).

Lipalo tsa sele ho tsoa moleng oa dorsal caudate le tsona li ile tsa hlahlojoa ho sebelisoa ANOVA ea mekhoa e meraro. Tlhahlobo ea pele e senotse ts'usumetso e kholo ea boiphihlelo ba pele ba thobalano kapa amphetamine palong ea lisele tse ntle tsa c-Fos. Ntle le moo, ha ho na tšusumetso ea boiphihlelo ba pele ba thobalano kapa amphetamine palong ea lisele tse hlalosang c-Fos e fumanoe cortex cortex e sebelisang ANOVA ea mefuta e 'meli (ya data e sa bontsitsoeng).

TŠOHLOA

Morero oa lipatlisiso tsena o ne o habeli. Re qalile ka ho hlahloba litlamorao tsa boiphihlelo ba thobalano liketsong tsa cellular maemong a fapaneng a li-nucleus. Khatiso ea bobeli, hore na boiphihlelo ba pele ba thobalano bo ka khotsofatsa tsela ea mesolimbic dopamine, e ile ea phenyekolloa ka ho bapisa likarabo tsa boits'oaro ba liphoofolo tse nang le thobalano le tsa bootsoa le ente ea amphetamine. Seo re se fumaneng ha se bontše feela hore boitšoaro ba basali ba thobalano bo ka kenya tšebetsong li-neuron bokong ba li-nucleus empa hape le hore boiphihlelo ba thobalano bo ka tsibosa likarabo tsa neuronal ho amphetamine.

Boitšoaro ba thobalano bo hlahisa polelo ea c-Fos khetla le mokokotlo oa li-nucleus

Teko ea boitšoaro ba thobalano e atolositse polelo ea c-Fos karolong ea mantlha, empa eseng khetla, ea tšehetso ea lipatlisiso tsa nalane e bonts'ang hore ketsahalo e le 'ngoe ea thobalano e ka kenya tšebetsong li-neuron ka har'a li-ligus tsa basali.Meisel et al., 1993; Joppa et al., 1995; Mermelstein le Becker, 1995; Pfaus et al., 1995; Kohlert et al., 1997; Kohlert le Meisel, 1999). Lingoliloeng tse sebetsanang le dichotomy e sebetsang ea li-nucleus li kopantsoe le litlaleho tse ngata tsa liphetoho tse fapaneng phetisong ea dopamine kahare ho khetla le konokono ea li-nucleus tsa karabelo ho arabela moferekong oa meriana le oa 'mele. Tsamaiso ea lithethefatsi tse 'maloa tsa tlhekefetso e fella ka keketseho e ikhethileng ea maemo a dopamine ea extracellular dollamine khetla ea li-nucleus accumbens (Pontieri et al., 1995; Nisell et al., 1997; Pierce le Kalivas, 1997a; Tanda et al., 1997; Tanda le Di Chiara, 1998; Barrot et al., 1999; Cadoni le Di Chiara, 1999). Ka mokhoa o tšoanang, lijo tse fumanehang habonolo (Tanda le Di Chiara, 1998; Di Chiara et al., 1999a; Kelley, 1999, khatello ea maikutlo (mohlala, ho thothomela ka maoto) (Kalivas le Duffy, 1995; Tidey le Miczek, 1997; Bruijnzeel et al., 1999; Wu et al., 1999), le boqapi ba tikoloho (Rebec et al., 1997;Rebec, 1998) hape khetha ka nepo phetiso ea dopamine khetla ea khubung ea li-nucleus.

Seo re se fumaneng se lumellana le monahano oa hore khetla le mantlha li sebetsa hantle, leha re fumane motheo, eseng khetla, ho arabela boits'oarong ba thobalano. Ho a khonahala, leha ho le joalo, ho bile le liphetoho phetohong ea c-Fos khetla ea li-nucleus accumbens, empa liphetoho tsena ha lia ka tsa bonoa. Khetla ena e hlophisitsoe ka mokhoa o ikhethileng hore e be likarolo tse fapaneng, "" "" "" "" "" "- Karolo ea 'mala, khubung le bokantle ba" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" Likaha tse ka hare le tse ka hare tsa khetla ea medali e ka ba likarolo tse ling tse peli tse ikhethileng (Groenewegen et al., 1999). Likarolo tsena tsa khetla, hammoho le likarolo tsa motsoako le tsa morao-rao li amohela mefuta e fapaneng ea likhakanyo tse tsoang libakeng tse kotloloho le tse bohlasoa.Groenewegen et al., 1999). Ho feta moo, e fumanehang kahara likarolo tsena tsa methapo ea kutlo e hlophisitsoeng ka likarolo tse ikhethileng tsa anatomical (Groenewegen et al., 1999). Hobane litlamorao tsa boitšoaro ba thobalano ho polelo ea c-Fos thutong ena li ile tsa hlahlojoa feela ho khetla ea dorsomedial, ho ka etsahala hore palo ea lisele tse ntle tsa c-Fos e hlile ea fetoha mofuteng o fapaneng oa khetla.

Leha ho na le tlhokomeliso ea hore mesebetsi e mengata ea li-nucleus e bokellanang e lebisitsoe sebakeng sa khetla, ho a utloahala ho nahana hore lipotoloho tse fapaneng tsa neural tse kahare tsa nucleus li kenella mefuteng ea matlafatso ea boits'oaro bo fapaneng. Carelli et al. (2000)e tlaleha haufinyane hore li-nucleus li bokella li-neuron ka har'a likhoto li bonts'a ts'ebetso e tšoanang ea li-neuronal nakong ea ts'ebetso e arabelang li-reinforcers tse peli tsa tlhaho (ke hore, lijo le metsi) empa mekhoa e fapaneng ea ho thunya nakong ea ho arabela ts'ebetso ea tlhaho ea ho matlafatsa le koae. Ba fihletse qeto ea hore li-circuits tse fapaneng tsa neural tse bokellaneng li sebetsa tlhahisoleseling mabapi le lijo le matlafatso ea metsi le phallo ea koae (Carelli le al., 2000).

Boiphihlelo ba botona le botšehali bo hlahisa phello ea polelo ea c-Fos ka mokokotlo oa "rostral-caudal axis" ea li-nucleus

Lingoliloeng tse hlahlobang mokhatlo oa nyutlelie ka rostral-caudal nucleus e nyane; leha ho le joalo, phapang e hlakileng ea tšebetso le ea sebopeho se bonoe. Seo re se fumaneng se lumellana hantle le liphuputso tse tlalehileng taolo e arohaneng ea likarabo tsa methapo ea kutlo le likoloi ka nqa eohle ea rostral-caudal axis. Cholecystokinin (CCK) ka tsela e fapaneng e hlophisa litlamorao tse tlisoang ke dopamine ho rostral le caudal nucleus accumbens (Crawley et al., 1985a,b), hyperlocomotion e susumetsang ea dopamine ha e kenngoa ka har'a li-caudal accumbens, e leng sebaka se kenyelletsoeng ke CCK neurons colocalized le dopamine (Crawley et al., 1985a,b; Lanca et al., 1998). Le ha ho le joalo, CCK ha e sebetse ka boits'oaro ha e kenngoe ka har'a rostral nucleus, sebaka se fumanang likhakanyo tsa CCK le dopamine.Crawley et al., 1985a,b; Lanca et al., 1998). Ho boetse ho tlalehiloe hore infusion e tobileng ea amphetamine ka har'a khetla ea rostral, khetla ea caudal, kapa mantlha e ama mesebetsi ea boits'oaro le li-dopamine tsa extracellular dopamine le serotonin (Heidbreder le Feldon, 1998). Taolo ea li-peptide tsa opioid, ntho P, dopamine D1 receptors (Voorn le Docter, 1992; Jongen-Relo et al., 1994b; Voorn et al., 1994), le tokollo ea acetylcholine (Jongen-Relo et al., 1995) ka dopamine le dopamine receptor agonists le tsona li fapana pakeng tsa likarolo tsa rostral le tsa caudal tsa li-accumbens, ha li-rostral accumbens li amehile haholo ho dopamine depletion le tsamaiso. Leha likhohlano tsena tse sebetsang pakeng tsa li-rostral le caudal nucleus li tlalehiloe, ke hobaneng ha likarohano tsena tse sebetsang li ntse li sa utloisisehe ka botlalo.

Boiphihlelo ba botona le botšehali bo hlahisa ketsahalo ea amphetamine-ikiwa

Liphetho tse tlalehiloeng mona le thutong ea pejana li khothaletsa hore boiphihlelo ba pele ba thobalano bo lematsa likarabo tsa neuronal tlhahlobo ea boitšoaro ba thobalano, e bonts'ang keketseho e nkoang ea tokollo ea dopamine (Kohlert le Meisel, 1999) le tšebetso ea maqhubu ho li-nucleus accumbens (thuto ena). Kameho e 'ngoe ke hore basali ba nang le boithuto thutong e fetileng ba ka be ba arabetse tlhahlobo ea boitšoaro ba thobalano le litloaelo tsa tikoloho hobane boiphihlelo ba thobalano le liteko li ne li etsoa ka kamoreng e le' ngoe. Lits'oants'o tsa tikoloho tse amanang le boits'oaro bo khothalletsoang li ka fumana thepa ea tšusumetso le ho eketsa maqhubu a dopamine ka har'a li-nucleus accumbens (Reid et al., 1996, 1998; Watson le Nyane, 1999). Kameho ea bobeli ke hore hobane mehato ea boits'oaro ba banna e ne e sa tlaleheloa, ha ho tsejoe hore na lihlopha tse peli tsa basali tse lekiloeng ho tsa thobalano li amohetse tšusumetso e lekanang ea tlhasimollo ea bosali. Ho tlalehiloe hore ho ts'oaroa ha vaginocervical ho hlokahala bakeng sa ho lokolloa ha dopamine ka har'a li-bokellase tsa nucleus nakong ea ho ruruha (Kohlert et al., 1997). Mohlomong basali ba nang le thobalano ba ile ba fumana tšusumetso e eketsehileng ea botšehali (e sa lekantsoeng thutong ena), ka hona, ba eketsa c-Fos induction. Ka hona, ho netefatsa ts'ebetso ea thobalano ea basali e khotsofatsa tsela ea mesolimbic dopamine, re fuputse hore na basali ba nang le tsebo ea thobalano le ba sa tsebeng letho ba arabile ka mokhoa o fapaneng ka ente ea amphetamine, e leng tšusumetso e 'ngoe e tsejoang ka ho kopanya litlamorao tsa eona ka tsela ea dopamine. Ntle le moo, ho netefatsa hore likarabo tse khahlisang li bonoa ka lebaka la boitsoaro bo kopanetsoeng ba thobalano eseng ka lebaka la ho tloaelana le tikoloho le boitšoaro ba thobalano, likarabo tsa boits'oaro ba hamphe ho amphetamine li ile tsa hlahlojoa tikolohong ea lipale.

Amphetamine e ile ea eketsa tšebetso e akaretsang ho li-hamsters tsohle tsa basali. Leha ho le joalo, basali ba nang le thobalano ba ile ba arabela kapele ho amphetamine ho feta basali ba batšehali ba kopanelang liphate. Liphetho tsena li netefatsa tšusumetso eo boitšoaro bo kopanang ba ho etsa thobalano bo ka utloisang methapo tseleng ea mesolimbic dopamine mme e fana ka tlhahiso ea hore liphetoho tseleng e hlahisang likarabo tsa boitšoaro bo susumetsoang molemong oa tlhaho le ts'usumetso ea psychomotor.

Liphumano tsena li lumellana le monahano oa hore ho na le mekhoa ea ho fetola likarabo tsa lithethefatsi le boitšoaro ba thobalano (Robinson le Berridge, 1993; Pierce le Kalivas, 1997b). Liphuputso tse 'maloa tsa morao-rao li hlokometse tšusumetso ea maikutlo lipakeng tsa ho pepesetsoa lithethefatsi khafetsa le boits'oaro bo khothalletsoang ba tlhaho. Matšoenyeho a ho hlola bophelo ba setjhaba a fokotsa nako ea ho ipusa ea koae ka likhoto (Tidey le Miczek, 1997). Tikoloho e ratoang ka ente ea morphine e pheta-phetoang e ka tsamaisa boitšoaro ba thobalano ho likhoto tsa banna (Mitchell le Stewart, 1990a,b). Amphetamine pretreatment e boetse e thusa boitšoaro ba thobalano ho likhoto tsa banna tse sa kopaneleng thobalano mme e hokahanngoe le tokollo ea dopamine e kholisitsoeng ka har'a li-nucleus accumbens (Fiorino le Phillips, 1999).

polelo ea c-Fos e ile ea sekasekoa ka har'a li-bokono tsa nucleus kamora kalafo ea amphetamine. Ho ile ha nahanoa hore amphetamine e ne e tla eketsa polelo ea c-Fos ka har'a li-bokellase tsa "nucleus", le ka tekanyo e kholo ho basali ba nang le bohlola. Leha ho le joalo, ha ho litlamorao tsa amphetamine palong ea lisele tse hlalosang c-Fos li fumanoe ho efe kapa efe ea likarolo tse ka tlase tsa li-nucleus accumbens. E bonahala ho tloha Tafoleng3 hore liphoofolo tse laolang tekong ea 2 (tse tšehali tse nang le letsoai) li ne li e-na le lisele tse ntle haholo tsa c-Fos bapisoa le liphoofolo tse laoloang tekong ea 1 (ha ho na liteko tsa basali). Badiani et al. (1998) e tlaleha hore lipalesa lia eketseha c-fos mRNA dikahare tsa bokellane ba nucleus e bokellana, le hore phello ena ea boqapi hoc-fos Litaba li ne li le matla libakeng tse ngata tsa boko hoo tsamaiso ea amphetamine tikolohong ea rialo e sa hlahiseng karabelo e eketsehileng ea tlatsetso. Kahoo, ho bonahala ho ka etsahala hore thutong ea rona khatello ea maikutlo a ho isoa tikolohong e ncha ea phaposi ea tlhahlobo e hlahisitsoeng ke protheine ea c-Fos, ka hona liphetoho tse hlakileng ponong ea c-Fos e susumetsoang ke amphetamine le boiphihlelo ba thobalano.

Tafole 3.

Bolele ± SEM palo ea basel ea lisele tse sa sebetseng tsa c-Fos tse bokellaneng li bokellana molemong oa ho laola liphoofolo litekong tsa 1 le 2

Bohlokoa bo ka bang teng

Liteko tsena li kena lenaneong le ntseng le hola la lithuto (Mitchell le Stewart, 1990b; Fiorino le Phillips, 1999; Miczek et al., 1999) e bonts'a hore liphihlelo tsa phoofolo li ka bonts'a karabelo ea tsela ea mesolimbic dopamine ka bobeli ho boits'oaro boo e leng karolo ea repertoire ea tlhaho ea phoofolo le lithethefatsi tse itseng tseo batho ba tsebahalang ka ho hlekefetsa (Bohlale le Bozarth, 1987). Taba e ka sehloohong phuputsong e mabapi le tšebeliso e mpe ea lithethefatsi ke ho ba kotsing ea motho ka mong litlamorao tsa lithethefatsi.Newcomb, 1992; Robinson le Berridge, 1993), mme boithuto bo bongata bo ka fana ka leseli mabapi le nts'etsopele ea bokhoba ba lithethefatsi ho batho.

Mongolo o botlaaseng ba leqephe

    • E amohetse June 8, 2000.
    • Tlhahlobo e amohetse December 12, 2000.
    • E amohetse December 20, 2000.
  • Patlisiso ena e tšehelitsoe ke National Science Foundation Grant IBN-9723876. Re leboha Melissa Zila, Shannon McCanna, Marchelle Baker, Michael Huntington, le Deborah Shelley ka thuso ea bona ea boithuto mabapi le boits'oaro ba tlhahlobo ea boitšoaro le c-Fos.

    Litaba tsa mangolo li lokela ho lebisoa ho Dr. Robert L. Meisel, Lefapha la Saense ea Psychological, Univesithi ea Purdue, West Lafayette, KA 47907-1364. Lengolo-tsoibila: [imeile e sirelelitsoe].

LITLHAHISO

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