Methamphetamine galue i luga o faʻafitauli o neu e faʻatonutonuina ai feusuaiga i tama tane (2009)

Neuroscience. 2010 Mar 31; 166 (3): 771-84. doi: 10.1016 / j.neuroscience.2009.12.070. Epub 2010 Jan 4.

Frohmader KS, Amata le J, Atamai poto, Lehman MN, Coolen LM.

puna

Matagaluega o Anatomy ma Cell Biology, Schulich School of Medicine and Dentistry, Iunivesite o Western Ontario, Lonetona, ON, Kanata, N6A 5C1.

lē faʻatino

Methamphetamine (Meth) o se mea e sili ona malosi e fai ma vaisu. O le faʻaleagaina o Meth e masani ona fesoʻotaʻi ma le faiga masani o tulaga lamatia o feusuaiga ma le faʻateleina o le faʻaogaina o le Human Immunodeficiency Virus and Meth e lipotia ai le faʻateleina o tuʻinanau feusuaʻiga, faʻanoanoa, ma le fiafia i feusuaiga. O le faavae o meaola mo lenei vailaau oona e le iloa. O suʻesuʻega o loʻo i ai nei o loʻo faʻaalia ai o le pulega a Meth i le tamaʻi tama e faʻaaogaina ai uʻamea i itu o le mafaufau o le mesolimbic system e aofia ai i le faatonutonuina o amioga tau feusuaiga. Aemaise lava, Meth ma le mating e mafai ona faʻamalosia ai sene i totonu o le tumutumu o le tumutumu ma le atigi gutu, amygdala, ma le coringx tua. O nei suʻesuʻega ua faʻamaonia ai, e ese mai i le talitonuga o loʻo iai i le taimi nei, o fualaau o le sauaina e mafai ona faʻaalia ai lava sela e pei o se faʻamalosi faalenatura, o amioga tau feusuaʻiga, ma o le a ono aʻafia ai le sailia malosi o lenei tau masani.

uputatala: nucleus accumbens, amygdala faʻamalositino, vailaau muamua, vailaau faʻaleagaina, toe gaosia, tagofia o mea ua fai ma vaisu

O le faʻamalosia ma le taui e faʻatonutonuina e le mesolimbic system, se fesoʻotaʻiga fesoʻotaʻi o vaega o faiʻai e aofia ai le vaega o le faʻaleleia o le vaʻalele (VTA) nucleus accumbens (NAc), amygdala, ma medial frontfront cortex (mPFC)Kelley, 2004, Kalivas ma Volkow, 2005). E tele molimau e faʻaaogaina ai le manolimbic i le tali atu i mea uma e lua o le sauaina (Di Chiara ma Imperato, 1988, Chang et al., 1997, Ranaldi et al., 1999) ma le natura o amioga faʻamalieina e pei o amioga feusuaʻi (Fiorino et al., 1997, Balfour et al., 2004). O amioga tau feusuaiga a alii, ma aemaise ai le faʻamalosia, e matua tauia ma faʻamalosia i faʻataʻitaʻiga o manu (Pfaus et al., 2001). O tamaʻi tootoo e atiina ae se nofoaga faʻasolosolo (CPP) e faʻafetaui (Agmo ma Berenfeld, 1990, Martinez ma Paredes, 2001, Tenk, 2008), ma o le a faʻatinoina galuega faʻapitoa e maua ai se avanoa i se fafine e faʻafeusuaʻi le faʻafeusuaiga (Everitt et al., 1987, Everitt ma Stacey, 1987). O fualaau o le faasaunoa e tauleleia ma faamalosia, ma o le a aoao e tagata manu e faʻaaoga mea e faʻaleagaina ai, e aofia ai le opiates, nicotine, ava malosi, ma le psychostimulants (Poto, 1996, Pierce ma Kumaresan, 2006, Feltenstein ma See, 2008). E ui lava e iloa uma o vailaʻau o le sauaina ma amioga feusuaʻi e faʻaaogaina ai le mafaufau o le mafaufau, e leʻo manino i le taimi nei pe o aʻafiaga o le faʻasaunoa e aʻafia ai laina tutusa lea e faʻatalanoa amioga tau feusuaʻiga.

Na faʻaalia e le electrophysiological studies o meaai ma cocaine o loʻo faʻagaoioia uma i totonu o le NAc. Ae ui i lea, e le o faʻamalosia e le aufaʻatasia e lua ia lava sene i totonu o le NAc (Carelli et al., 2000, Carelli ma Wondolowski, 2003). E le gata i lea, o meaai ma le sologa lelei o le pulea e le tagata lava ia e le mafua ai suiga umi o meatotino eletise e pei ona aʻafia ai e le kokeni (Chen et al., 2008). I le eseesega, o se aofaʻiga o faʻamaoniga e taʻu mai ai o amioga tane feusuaʻiga ma fualaau o le sauaina e ono mafai ona galue i luga o ia mesolimbic neurons. Psychostimulants ma opioids e suia le faʻaalia o uiga feusuai i tama tane (Mitchell ma Stewart, 1990, Fiorino ma Phillips, 1999a, Fiorino ma Phillips, 1999b). O faʻamatalaga lata mai nei mai la matou suʻesuʻega na faʻaalia ai o aafiaga tau feusuaiga e suia ai le tali atu i psychostimulants e pei ona molimauina e se tali maualuluga tali tali ma lagona lelei taui ile d-amphetamine ile meaola masani (Pitchers et al., 2009). O se tali talitutusa na maitauina talu ai ona o le faʻaalia o le amphetamine poʻo isi vailaʻau faʻatauāina (Lett, 1989, Shippenberg ma Heidbreder, 1995, Shippenberg et al., 1996, Vanderschuren ma Kalivas, 2000). Faʻatasi, o nei suʻesuʻega ua fautua mai ai o amio feusuaʻi ma tali i fualaau faasaina o le faʻaleagaina e faʻasalalauina e le ova tutusa i le mesolimbic system. O le mea lea, o le sini muamua o le suʻesuʻega nei o le suʻesuʻeina lea o le faʻafouina o le mesolimbic e ala ile amio feusuaʻi ma le faʻamalositisi i le mea lava e tasi. Aemaise lava, na matou suesueina le manatu e faapea, o le psychostimulant, methamphetamine (Meth), e galue tuusaʻo i luga o neu e masani ona faʻasalalau amioga tau feusuaʻiga.

O Meth o se tasi o vailaau faʻasaina e sili ona faʻaleagaina i le lalolagi (NIDA, 2006, Ellkashef et al., 2008) mama e masani lava ona fesootaʻi atu i amio feusuai faatautala. O le mea e maofa ai, o le faʻaaogaina e le au Meth le faʻateleina o le manaʻoga feusuaiga ma le faʻanofo, faʻapea foi ma le faʻaleleia o le fiafia i feusuaiga (Semple et al., 2002, Schilder et al., 2005). E le gata i lea, O le faʻaleagaina o Meth e fesoʻotaʻi faʻatasi ma amioga faʻafeusuaiga (Rawson et al., 2002). E masani ona faʻaalia e le au faʻapitoa le anoanoai o paaga feusuaʻi ma e itiiti le faʻaaogaina o puipuiga nai lo isi faʻatau fualaau faasaina (Somlai et al., 2003, Springer et al., 2007). O le mea e leaga ai, o suʻesuʻega e faʻamaonia ai Meth e faʻaaogaina e fai ma faʻamatalaga o amioga faʻafeusuaʻiga tau feusuaʻiga e faʻamapulaʻa ona latou faalagolago i lipoti e le faʻamaoniaina e le tagata lava ia (Elifson et al., 2006). O le mea lea, o se suʻesuʻega i le telefoni feaveaʻi o suiga Meth-induced i amioga tau feusuaʻiga i se meaola manu e manaʻomia mo le malamalama i lenei vailaʻau faʻamalosi faʻamalosi.

I le silasila i molimau o loʻo i luga o loʻo faʻamaonia ai o fualaau faasaina, aemaise lava Meth, e mafai ona galue i luga o neu masani e aofia i le faʻatalanoaina o amioga tau feusuaiga, o le faʻamoemoe o le suʻesuʻega nei o le suʻesuʻeina o le faʻafouina o le tino e ala i feusuaiga ma le puleaina o le psychostimulant Meth. O lenei suʻesuʻega na faʻaaogaina ai se metotia faʻanatura, e faʻaaogaina ai le faʻamalosia o le kemikolo e faʻaalia ai vave fatuga o le Fos ma phosphorylated Map Kinase (pERK) e faʻamaonia ai le faʻaosoina o le neural faʻatasi e ala i amioga tau feusuaiga ma Meth. Fos e na o le faʻaalia i totonu o le siama o sela, faatasi ai ma se faʻamaoniga maualuga o le 30-90 minute pe a uma le faʻamalosia o le neuron. E tele faʻamaoniaga o gaoioiga feusuaʻiga e faʻaosofia ai le Fos expression i le mafaufau (Pfaus ma Heeb, 1997, Veing and Coolen, 1998), e aofia ai le mesocorticolimbic system (Robertson et al., 1991, Balfour et al., 2004). E iai foi faʻamaoniga o fualaau o le faʻaleagaina e faʻaalia ai le pERK i totonu o le mesocorticolimbic system (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005). I le faatusatusa atu i le faaupuga Fos, phosphorylation o le ERK o se faagasologa sili ona manaia ma e na o le 5-20 minute e maeʻa pe a maeʻa le faʻamalosia o le neuronal. O faʻamatalaga manino faaletino o le Fos ma le PERK ua avea ai i latou ma seti o faailoga mo le toe faʻamalosia mai o le neuronal mulimuli ane e ala i fua eseese e lua.

FUAFUAGA FAATINO

Mataupu

Ole tama matua Sprague Dawley (210-225 g) na maua mai Charles River Laboratories (Montreal, QC, Kanata) na tuʻuina i totonu o le lua pusa i plexiglas cages (cages). Sa tumau le potu manu i se 12 / 12 h i le liua o le uila (moli i le 10.00 h). Sa maua meaai ma vai ad libitum. O faʻataʻitaʻiga uma na faia i le afa muamua o le vaega o le pouliuli i lalo o le malamalama mumu mumu. O fua o fafine na faʻaaogaina mo amioga tau feusuaʻiga na faʻapipiʻiina i lalo o le loloto o le faʻafeusuaiga (13 mg / kg ketamine ma le 87 mg / kg xylazine) ma maua ai se iniseti subcutaneous e aofia ai le 5% estradiol benzoate (EB) ma le 95% cholesterol. O le taliaina o feusuaiga na mafua mai i le soona fai (sc) le puleaina o 500 μg i le 0.1 ml suauu sesame 4 h i luma ole suʻega. O taualumaga uma na faʻamaonia e le Komiti o Tausiga o Manu i le Iunivesite o Western Ontario ma ia o gatasi ma taʻiala a le Kanata Kanata mo le tausiga o manu.

Faʻailoga Faʻataʻitaʻiga

Faʻataʻitaʻiga 1 ma 2: Na faʻatagaina tamaʻi tama (n = 37) e feiloaʻi ma se fafine e talileleia i se tasi ejaculation (E) poʻo le 30 min, lea na muamua oʻo mai i le eletise mama (60 × 45 × 50 cm) i le lima faalua -solosolo taimi aʻo leʻi faia le suʻega, ina ia maua se faʻafeusuaiga. A o faagasolo nei vasega e lua, o faʻamaumauga uma mo le faia o feusuaʻiga na faʻamaumauga, e aofia ai le: faʻamalologa o le taʻaloga (ML, taimi mai le faʻasagaga o le fafine seia oʻo i le mauga muamua), faʻalavelave faʻalavelave (IL; taimi mai le faʻavaeina o le fafine seia oʻo i le mauga muamua o le gaioculation letency (EL, taimi mai le faʻamaʻi muamua i le feʻaveaʻi), faʻasologa o le taimi ejaculation (PEI, taimi mai le faʻasologa i le faʻamaʻi muamua), numera o le maualuga (M), ma le numera o le faʻasaina (IM) (Agmo, 1997). Na maua uma e alii le 1 ml / kg i aso taitasi o le iniseti 0.9% NaCl (saline; sc) 3 aso sosoo ao leʻi oʻo i le aso o le suʻega, mo le masani ile tagofiaina ma inisiua. I se tasi aso ao lumanai le aso o le suʻega, e nofofua uma alii nofofua. I tamaʻitaʻi faʻapitoa, e mafai ona faʻamalosia Fos e ala i faʻamatalaga faʻapitoa o fesoʻotaiga e fesootaʻi ma le masaniga faʻafeusuaʻiga muamua (Balfour et al, 2004). O le mea lea, o faʻataʻitaʻiga uma ma faʻataʻitaʻiga i le taimi o suʻega mulimuli sa faia i le fale ole fale (aloese mai i tulaga o mea e fai ai fua) ina ia taofia ai le faʻatinoina o le faʻatoagaina i le tane le pulea. Na tufatufaina atu alii i ni vaega faataitai se valu e le eseese i soo se ituaiga o feusuaʻiga i le taimi o le lua (2) faʻatalanoaga. I le suega faaiʻu, e mafai ona faʻatagaina tane i le fale o le fale seia oʻo ina latou faʻaalia se feusuaʻiga (feusuaiga) pe leai foi se paaga tamaʻitaʻi (leai se feusuaiga). O tamaʻitaʻi uma na faʻauʻuina le 60 minute mulimuli ane i le amataga o le mating ina ia mafai ai ona faʻatalanoaina le Fos-expression faʻaipoipoga. Na maua e alii se tui o le 4 mg / kg Meth poo le 1 ml / kg saline (sc) (n = 4 taitasi), 10 (experiment 1) poʻo 15 (experiment 2) min aʻo leʻi faʻauʻuina, mo le suʻesuʻeina o le phosphorylation faʻataʻitaʻiina. MAP kinase. O le faʻasologa ma le taimi ao le i faʻataunuʻuina na faavae i lipoti talu ai (Choe et al., 2002, Choe ma Wang, 2002, Chen ma Chen, 2004, Mizoguchi et al., 2004, Ishikawa et al., 2006). O vaega e pulea e aofia ai tane e leʻi pagatia, ae na maua Meth 10 (n = 7) poʻo 15 (n = 5) min ae leʻi faia le taulaga, poo le iniseti 10 (n = 5) poʻo le 15 (n = 4) min ae lei faia le taulaga . I le mulimuli ai i taulaga, na faia ai masini mo le immunohistochemistry.

Faʻataʻitaʻiga 3: Talu ai sa faʻaaogaina le maualuga o Meth i le faʻataʻitaʻiga 1 ma le 2, na faia ai se suʻega faʻa-neuroanatomia faʻapitoa e suʻesuʻe ai pe afai o amioga feusuaʻi ma se fua maualalo o le Meth e faʻaaogaina ai fua faatatau o le faʻaaogaina o le neural activation. O lenei suʻesuʻega na faia i se auala tutusa e pei o 1 ma 2 faʻataʻitaʻiga. Ae ui i lea, i le suega mulimuli, o matai ma le le mautonu (n = 6 taitasi) na maua le 1 mg / kg Meth (sc) 15 min ao leʻi faia le taulaga.

Faʻataʻitaʻiga 4: Faʻataʻitaʻi pe o le faʻafouina o le neura e mafua mai i feusuaiga ma Meth e patino mo Meth, o lenei suʻesuʻega na suʻeina pe o mamanu tutusa o le toe faʻafouina o le neura e mafai ona vaaia i le psychostimulant d-amphetamine (Amph). O lenei faʻataʻitaʻiga sa faia i se tulaga tutusa e pei o 1 ma 2 faʻataʻitaʻiga. Ae ui i lea, i le suega mulimuli, na pulea tama tane poo Amph (5 mg / kg) poʻo le saline (1 mg / kg) (sc) 15 min ao le i faia le taulaga (n = 5 taʻitasi). Puleaina o tane e leʻi faʻaaogaina na maua ni saline poʻo Amph 15 minute ao leʻi faia le taulaga. O se aotelega o vaega faataitai na faʻaaogaina i suʻega 1-4 ua tuʻuina atu Laulau 1.

Laulau 1       

Aotelega o vaega faʻataʻitaʻiga na aofia ai i suʻega 1-4.

Laʻasaga sauniuni

O manu na faʻaaogaina i le pentobarbital (270 mg / kg; ip) ma faʻapipiʻi faʻatasi ma 5 ml o saline mulimuli mai le 500 ml 4% paraformaldehyde i le 0.1 Msphate buffer (PB). Sa aveeseina masini ma toe faatulaga mo le 1 h i le vevela o le potu i le mea lava e tasi, ona faatofuina lea i le 20% sucrose ma le 0.01% Sodium Azide i 0.1 M PB ma teuina i le 4 ° C. Vaega o le Coronal (35 μm) na tipi i luga o se masini miti malulu (H400R, Micron, Siamani), na aoina i ni auala se fa i le solution cryoprotectant (30% sucrose ma le 30% ethylene glycol i 0.1 M PB) ma teuina i le 20 ° C seia oʻo i le isi gaosiga.

Immunohistochemistry

O faʻafiafiaga uma na faia i le vevela o le potu ma le faʻamafanafanaga lemu. O fuālaʻau faʻapitoa na mulumuluina faʻatasi ma le 0.1 M Phosphate-o le saline ua faʻafefete (PBS) i le va o incubations. Na faʻaaogaina vaega i le 1% H2O2 mo le 10 min, ona pupuni lea i le fofo faʻasusu (PBS o loʻo i ai le 0.1% vailaʻau o le vevine albumina ma 0.4% Triton X-100) mo 1 h.

PERK / Fos

O le tagata na fausiaina i le po faatasi ma le antibody anticlonal antibody against p42 ma le p44 map kinases ERK1 ma le ERK2 (pERK; 1: 400 faʻamatalaga 1 vili 19; 1: 4.000 faʻamatalaga 2 ma le 3 vili 21; Cell Signaling Cat # 9101;), sosoo ai ma 1 H incubations faʻatasi ai ma le IgG-anti-rabbit IgG (1: 500; Jackson Immunoresearch Laboratories, West Grove, PA) ma le avidin-horseradish peroxidase complex (ABC Elite; 1: 1000 Vector Laboratories, Burlingame, CA). Ona faʻapipiʻi lea o le tino mo le 10 min ma le bioramene tyramide (BT; 1: 250 i PBS + 0.003% H2O2; Faʻamaumauga o le Amplification Signal, NEN Life Sciences, Boston, MA) ma le 30 min ma le strepavidin conjugated strepavidin Alexa 488 (1: 100, Jackson Immunoresearch Laboratories, West Grove, PA). O le isi, o le mea na fafaguina i le po faatasi ai ma le anti-polyclonal rabbit against c-Fos (1: 500, SC-52, Santa Cruz Biotechnology, Santa Cruz, CA), sosoo ai ma le 30 min incubation ma le lapisi rabbit Alexa 555 (1: 200, Jackson Immunoresearch Laboratories, West Grove, PA). Ina ua maeʻa, na fufulu lelei vaega i le 0.1 M PB, faʻaofuofu i luga o faʻatalama tioata ma 0.3% gelatin i ddH20 ma ufiufi i le masini eletise (Gelvatol) o loʻo i ai le antane fading 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). O le faʻamalosia o le kemikolo e aofia ai le le faʻamaonia o se tasi poʻo le lua o mea faʻapitoa faʻatautau, e mafua ai le leai o se faʻamaumauga ile umi o le galu talafeagai.

Faʻamaumauga o Fuainumera

Feusuaiga

Mo faʻataʻitaʻiga uma e fa, o faʻamaumauga masani mo le faia o feusuaʻiga na faʻamaumauga e pei ona faʻamatalaina i luga ma auiliiliina e ala i le faʻaaogaina o iloiloga o le feteenaiga (ANOVA). Faʻamaumauga o faʻamatalaga o amioga feusuaʻi i le aso o le suʻega mulimuli na faʻaalia ai leai se eseesega taua i le va o vaega i soo se vaega o faʻataʻitaʻiga feusuaiga.

PERK / Fos Cell Counts

Sela e tasi ma le lua ona o le Fos ma le PERK na faitauina i le paluga o le NAc ma le atigi vaitaele, amygdala (BLA), o le plarodorsal medial amygdala (MEApd), le amygdala centrale (CeA), le medial preoptic nucleus (MPN), postromedial and tapuni o le moega o tua o le stria terminal (BNSTpm ma BNSTpl), ma le nofoaga o loʻo faʻamatuʻuina (ACA), prelimbic (PL), ma infralimbic (IL) sousregiona a le mPFC. O ata na puʻeina e faʻaaogaina ai le kamera CCD mafanafana (microfire, optronics) faʻapipiʻi i le microscope leica (DM500B, Leica Microsystems, Wetzlar, Siamani) ma le komepiuta Neurolucida (MicroBrightfield Inc) faʻatasi ai ma faʻapipiʻi kamera tumau mo mataupu uma (faʻaaoga sini 10x). I le faʻaaogaina o le komepiuta neurolucida, o vaega o auʻiliʻiliga na faʻamatalaina faʻavae i luga o faʻailoga (Swanson, 1998) tulaga ese mo vaega o faiʻai taitasi (tagai Ata 1). O nofoaga masani o le auʻiliʻiliga sa faʻaaogaina i vaega uma sei vagana ai le NAc ma le atigi. I vaega mulimuli, o le PERK ma le Fos expression e le tutusa ma e foliga mai i mamanu tutusa. O le mea lea, o le autu atoa ma le atigi na faʻamatalaina e faavae i luga o faailo (vaʻalele i luga, lalata muamua, ma motu o Calleja). O vaega o le auiliiliga e le eseese i le va o vaega faataitai, ma o 1.3 mm2 i totonu o le NAc ma le atigi. O nofoaga masani o le auiliiliga mo nofoaga o loʻo totoe: 1.6 mm2 i le BLA, 2.5 ma le 2.25 mm2 i le MEApd ma le CeA, 1.0 mm2 i le MPN, 1.25 mm2 i le tulafono a le BNST ma le mPFC, ma le 3.15 mm2 i le VTA. E lua ni vaega na faitauina faʻapitoa mo vaega taitasi o le faiʻai i meaola taitasi, ma le aofaʻi o sela e tasi ma lua taulaina mo le PERK ma le Fos ma le pasene o sene PERK na faʻaalia le Fos marker. Mo faʻataʻitaʻiga 1, 2, ma 4, o faʻatulagaga o vaega na faʻatusatusa i le faʻaaogaina o auala e lua ANOVA (faʻamatalaga: mating and drug) ma le LSD Fisher mo faʻailoga faatusatusaga i se tulaga taua o 0.05. Mo le faʻataʻitaʻiga 3, na faʻatusatusa avega faʻavae i le faʻaaogaina o t-suʻega i se tulaga taua o le 0.05.

Ata 1       

Fuafuaga faʻataʻitaʻi ma ata e faʻaalia ai vaega o faiʻai o auiliiliga. O vaega o auʻiliʻiliga na faʻaalia na faʻavae i luga o faʻailoga tulaga ese mo vaega o faiʻai taitasi, e leʻi eseese i le va o vaega faʻapitoa, ma e 1.25 mm2 i lalo o tulafono laiti a le mPFC (a), 1.3 mm2 i le ...

Images

Ata faʻapitoa mo Ata 3 na pueina i le faʻaaogaina o le kamera DCD (DFC 340FX, Leica) faʻatasi i le microscope leica (DM500B) ma na faʻapipiʻi mai i le Adobe Photoshop 9.0 software (Adobe Systems, San Jose, CA). O ata e leʻi suia i soo se auala vagana ai le fetuunaiga o le susulu.

Ata 3       

O ata o le vaega o le NAC na vave faʻasaina mo Fos (mumu; a, d, g, j) ma le pERK (green; b, e, h, k) o manu o vaega faʻapitoa taʻitasi: Leai Sex + Sal (a, b, c) , Sex + Sal (d, e, f), E leai se feusuaiga + Meth (g, h, i), ma le Sex + Meth (j, k, l). O vaega saʻo o ...

TULAFONO

Faʻafouina Neural of the Limbic System e le Faʻafeusuaiga Faʻafeusuaiga ma Meth Administration

Faʻataʻitaʻiga 1: Iloiloina o sela e tasi ma lua taulaina mo ni tane na maua Meth 10 minute ao leʻi faia le taulaga na faʻaalia ai Fos i totonu o MPN, BNSTpm, NAc core and shell, BLA, VTA, ma sousregiona uma o le MPFC, faʻatasi ai ma suʻesuʻega muamua e faʻaalia ai faʻamatalaga Fos i totonu o nei vaega (Baum ma Everitt, 1992, Pfaus ma Heeb, 1997, Veing and Coolen, 1998, Hull et al., 1999). Meth administration 10 minute ao le i faia le osigataulaga PERK i totonu o le NAc ma le atigi, BLA, MeApd, CeA, BNSTpl, ma itulagi o le mPFC, faʻatasi ai ma mamanu e faʻaosofia e isi psychostimulants (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005).

E le gata i lea, e tolu mamanu o le faʻauigaina o le faʻafouina o le neura i amio feusuaʻiga ma Meth na matauina: Muamua, o vaega o faiʻai na iloagofie pe o fea e faʻaaogaina ai feusuaiga ma fualaau faʻasolo e leai ni mea e faʻaogaina ai tagata (Laulau 2). Faʻapitoa lava, i le CeA, MEApd, BNSTpl, ma mPFC, faʻateleina siitaga i fualaʻau uma-faʻatosina PERK (F (1,16) = 7.39-48.8; p = 0.015- <0.001) ma feusuaʻiga-faʻaosofia Fos (F (1,16, 16.53) = 158.83–0.001; p <1,16) na maitauina. Peitai, i nei itulagi e leai se taua faʻaopoopoina i itulua faʻailogaina neurons i feusuaʻi Meth-togafitia tama. Pau lava le tuʻufaʻatasi o le MEApd, lea na maua ai le aʻafiaga o le faʻaipoipoga i luga o numera o sela lua faʻaigoa (F (9.991) = 0.006; p = XNUMX). Peitai, e leai se aotelega aʻafiaga o fualaʻau togafitiga ma lua faʻailoga i Meth togafitia kulupu sa le sili atu maualuga maualuga atu i saline togafitia kulupu, o lea sa le mafua mai i le vailaʻau (Laulau 2). Lona lua, o vaega o faiʻai na faʻamautuina pe o fea na faʻamalosia ai le faʻafouina o pepe e ala i le faʻaipoipo (Laulau 3). Aemaise lava, o le MPN, BNSTpm, ma le VTA na faatoa faʻaaogaina e ala ile matua, ma aofia ai le tele o faʻaopoopoga Fos (F (1,16) = 14.99-248.99; p ≤ 0.001), ae leai PERK Meth-induced.

Laulau 2       

Aotelega o faʻamatalaga o le PERK ma le Meth i totonu o potu faiʻai lea e faʻafeiloaʻi ai e le faʻafeusuaiga ma fualaau faʻasaina le faitau aofaʻi o tagata.
Laulau 3       

Aotelega o faʻamatalaga o le PERK faʻatasi ma le Meth-induced expression i vaega o faiʻai lea na faʻamalosia ai le faʻafouina o le toto e na o matame.

Mulimuli ane, na maua vaega o faiʻai i le mea e faʻaaogaina ai feusuaʻiga ma fualaau faʻasolosolo o le aofaʻi o le neurons (Ata 2 ma Ma3) .3). I le NAc autu ma atigi, BLA, ma le ACA, sa i ai aotelega aʻafiaga o le faʻaipoipo (F (1,16) = 7.87-48.43; p = 0.013- <0.001) ma togafitiga fualaʻau (F (1,16) = 6.39- 52.68; p = 0.022- <0.001), faʻapea foʻi ma fegalegaleaiga i le va o nei mea taua e lua (F (1,16) = 5.082-47.27; p = 0.04- <0.001; leai se taua fegasoloaʻiga i le ACA) i numera o sela faʻaalia uma fos-faʻaoso Fos ma Meth-faʻaosoina PERK. O le suʻesuʻega o le post hoc na faʻaalia ai, o numera o taʻilua ua faʻaigoaina o neo, na sili atu le maualuluga o aliʻi na aʻoaʻoina i le Meth pe a faʻatusatusa i le metate metotia e togafitia (p = 0.027- <0.001), poʻo le saline saline-treated (p = 0.001- <0.001) male (Ata 2 ma Ma3) .3). Ina ua faailoa mai faamatalaga e pei o pasene o fualaau faasaina, 39.2 ± 5.3% i le NAc, 39.2 ± 5.8% i le NAc shell, 40.9 ± 6.3% i le BLA, ma le 50.0 ± 5.3% o le ACA neurons na faʻaaogaina e e le gata i le tane ma le Meth.

Ata 2       

Fetufaaiga faʻafeusuaiga Fos ma Meth-faʻailoga pERK i le NAc, BLA, ma le ACA faʻaoso 10 min i le maea ai o le pulega o le 4 mg / kg Meth. O le fuainumera o le afa o Fos (a, d, g, j), pERK (b, e, h, k), ma le lua (c, f, i, l) o loo i totonu o le NAc core (a, ...

O se mea e le i mafaufauina o le amioga feusuaiga na aafia ai le MER-induced pERK. E ui na taua tele le Meth i le maualuga o le PERK i vaega uma o le Meth-injected male matai, i le NAc, BLA, ma le ACA, o le labeling PERK na sili atu ona maualalo i tane matai Meth-injected pe a faʻatusatusa i tamaʻi Meth-injected (Ata 2b, e, h, k; p = 0.017- <0.001). O lenei sailiiliga e mafai ona lagolagoina atili ai le manatu e faapea, o feusuaiga ma vailaau e galue i luga o laina tutusa, ae e mafai foi ona iloga o suiga i le gaosiga i le gaosia o fualaau faasaina po o le metabolism lea o le a mafua ai ona suia tali tali mai ia Meth. Ina ia suʻesuʻeina pe afai o amioga tau feusuaʻiga e mafua ai se mamanu faaletino o le faʻamalosia o fualaau faʻamaina, o vaega o le NAc, BLA, ma le ACA na faʻamaʻaʻaina mo alii na ositaulagaina i se taimi mulimuli ane (15 min) i le faʻamautuina o fualaau (faʻataʻitaʻiga 2).

Faʻataʻitaʻiga 2: Faʻamaumauga o sela se tasi ma le lua na faʻamaonia ai faʻamatalaga na faʻamatalaina i luga o amioga feusuaʻiga ma le faʻafeiloaʻi mulimuli ane i Meth 15 minute ao leʻi faia le taulaga na mafua ai le faateleina o le faateleina o Fos ma pERK immunolabeling i le NAc core and shell, BLA, and ACA. E le gata i lea, na maua foi i nei vaega ni faʻasalalauga taua o le Pos ma le Meth-induced pERK.Ata 4; aafiaga o le faʻaipoipoga: F (1,12) = 15.93–76.62; p = 0.002- <0.001; aafiaga o vailaʻau: F (1,12) = 14.11-54.41; p = 0.003- <0.001). Aofai o lua faʻailogaina neurons i feusuaʻi tama-ua tuiina tama na sili atu le maualuga faʻatusatusa i le metotia Meth-togafitia (p <0.001) poʻo faʻatasi saline-togafitia (p <0.001) tama. Ina ua faʻamatalaina faʻamatalaga o pasene o fualaʻau-faʻagaoioia neurons, 47.2 ± 5.4% (NAc autu), 42.7 ± 7.6% (NAc atigi), 36.7 ± 3.7% (BLA), ma 59.5 ± 5.1% (ACA) o neurons faʻagaoioia e le faʻaipoipoga na faʻagaoioia foi e Meth. E le gata i lea, o fualaʻau faʻatosina mai fualaʻau e leʻi eseʻese i le va o ulugaliʻi ma manu e leʻi feola (Ata 4b, e, h, k), i eria uma vagana ai mo le ACA (p <0.001). O nei faʻamaumauga o loʻo faʻailoa mai ai, o amioga tau feusuaʻiga e mafua ai le suia o le faiga masani o le PERK induction e le Meth.

Ata 4       

Fetufaaiga faʻafeusuaiga Fos ma Meth-faʻailoga pERK i le NAc, BLA, ma le ACA faʻaoso 15 min i le maea ai o le pulega o le 4 mg / kg Meth. O le fuainumera o le afa o Fos (a, d, g, j), pERK (b, e, h, k), ma le lua (c, f, i, l) o loo i totonu o le NAc core (a, ...

Faʻafouina Neural i le mulimuli i amioga feusuai ma le 1 mg / kg Meth

O nei taunuuga ua faaalia ai o amio feusuaiga ma le 4 mg / kg Meth ua faʻaaogaina le faitau aofaʻi o neurons i le NAc core and shell, BLA, ma ACA. To suʻesuʻeina le aʻafiaga o fualaau oona i luga o lenei mea i le faʻatoaagaina, o mamanu o le faʻafouina o le neural sa suʻesuʻeina foi e faʻaaogaina ai le fua maualalo ole Meth. O le NAc core ma shell, BLA, ma ACA na suʻeina mo le faʻatoagaina mai e le faʻafeusuaiga ma Meth. O le mea moni, amioga faʻafeusuaiga ma le mulimuli atu i le Meth na mafua ai le faateleina o le faateleina o Fos ma pERK faʻamaonia i le NAc ma le atigipusa atigipusa, le BLA, faʻapitoa foi i le vaega ACA o le MPFC (Ata 5). O le mea e malie ai, o le fua maualalo ifo o le Meth na mafua ai le tutusa o numera o le pERK o loʻo faʻailogaina ni neurons e pei ona faʻaosoina e le 4 mg / kg Meth i vaega o faiʻai e fa na suʻesuʻeina. O le mea e sili ona taua, o le NAc core ma shell, BLA, ma ACA na faʻaalia le faateleina o le faateleina o le aofaʻi o lua (lua)Ata 5c, f, i, l) faʻatusatusa i le male metotia Meth-injected male (p = 0.003- <0.001). Ina ua faʻamatalaina faʻamatalaga o pasene o fualaʻau-faʻagaoioia neurons, 21.1 ± 0.9% ma le 20.4 ± 1.8% i le NAc autu ma atigi faʻavae, 41.9 ± 3.9% i le BLA, ma 49.8 ± 0.8% o ACA neurons na faʻagaoioia e feusuaiga. ma Meth.

Ata 5       

Fetufaaiga faʻafeusuaiga Fos ma Meth-faʻailoga pERK i le NAc, BLA, ma le ACA faʻaoso 15 min i le maea ai o le pulega o le 1 mg / kg Meth. O le fuainumera o le afa o Fos (a, d, g, j), pERK (b, e, h, k), ma le lua (c, f, i, l) o loo i totonu o le NAc core (a, ...

Faʻaleagaina o Neural i le mulimuli i amio feusuaʻi ma le puleaina o le d-Amphetamine

Ina ia suʻesuʻeina pe o mea na maua i luga e patino mo Meth, o se suʻesuʻega faaopoopo na faʻatautaia e suʻesuʻe ai matāʻupu- ma le faʻafouina o le faʻaogaina ole uʻu. O le suʻesuʻega o sela e tasi ma lua taulaina mo le PERK ma le Fos na faʻaalia ai amioga faʻafeusuaiga ma le mulimuli atu i Amph na mafua ai le faateleina o le faateleina o Fos ma pERK immunolabeling i le NAc core and shell and BLA (Ata 6; aafiaga o le faʻaipoipoga: F (1,15) = 7.38-69.71; p = 0.016- <0.001; aafiaga o vailaʻau: F (1,15) = 4.70-46.01; p = 0.047- <0.001). E le gata i lea, o numera o lua faʻaigoaina o neo na sili atu le maualuga i le faʻaipoipoga Amph-faʻatusatusa i le le faʻafefiloiina Amph-treated (p = 0.009- <0.001), poʻo le masine saline-treated (p = 0.015- <0.001) tama (Ata 6c, f, i). Aʻo faʻamatalaga faʻamatalaga o pasene o fualaau faʻamalosi, 25.7 ± 2.8% ma 18.0 ± 3.2% i le NAc ma le gutu taʻitasi, ma 31.4 ± 2.0% o le BLA neurons na faʻaaoga e mating ma Amph. O le ACA o le MPFC na faʻaalia ai le maualuga o Fos faʻaaogaina i le mating (Ata 6j; F (1,15) = 168.51; p <0.001). Ae ui i lea, e le pei o le Meth, Amph e leʻi iʻu ai i le faʻateleina o siitaga i fualaʻau-faʻatupuina tulaga PERK i le ACA (Ata 6k) poʻo numera o nūmera e lua faʻamau i le ACA (Ata 6l) pe a faʻatusatusa atu i tamaʻitaʻi matai ma e leai ni maʻi.

Ata 6       

Faʻafeiloaʻiga feusuaʻiga Fos ma Amph-faʻailoga pERK i faʻamaumauga NAc, BLA, ma ACA 15 min pe a maeʻa le pulega o le 5 mg / kg Amph. O le fuainumera o le afa o Fos (a, d, g, j), pERK (b, e, h, k), ma le lua (c, f, i, l) o loo i totonu o le NAc core (a, ...

TALANOAGA

Ole suʻesuʻega o loʻo i ai i le taimi nei o loʻo faʻaalia i le maualuga o le telefoni feaveaʻi i le va o le faʻafouina o le neural activation e le amio faʻamalosia ma le psychostimulant Meth. O le mea lea, o nei faʻamatalaga e faʻaalia ai e le gata o faʻamalositino e galue i luga o le tasi lava itu o faiʻai e pulea ai taui masani, ae o le mea moni, o fualaau faʻamalosi e faʻagaoioia ia lava sene e aofia ai i le tulafono faatonutonu o taui masani. Aemaise lava, na faaalia iinei o amio feusuaʻiga ma Meth na faʻamalosia le faitau aofaʻi o neu i le NAc core ma shell, BLA, ma le ACA o le mPFC, faʻamautu nofoaga e mafai ai e Meth ona aʻafia amioga tau feusuaiga.

O le sailiga o loʻo iai i le taimi nei, o amioga feusuaʻiga ma le faʻaleleia o Meth e faʻaaogaina ai le faitau aofaʻi o neurons i le NAc, BLA, ma le ACA, e ese mai i faʻamaumauga mai isi suʻesuʻega e faʻaalia ai le tele o fuainumera o NAM Neo e faʻasaʻo ai le fualaau faasaina ma taui faalenatura.

Aemaise lava, o suesuega o le electrophysiology e faatusatusaina le faatoagaina o le toto i le taimi o le pulea e le tagata lava ia o taui masani (meaai ma vai) ma cocaine oona e faaalia ai o le puleaina o le cocaine na amataina ai se eseesega, le tele o le faitau aofaʻi o neu e masani ona le tali atu i le taimi e tali ai le tagata ma le faʻamalosia o meaʻai (92%). Naʻo le 8% o le faʻaaogaina o neu na faʻaalia ai le toe faʻaleleiaina e le cocaine ma le taui masani (Carelli et al., 2000).

I le eseesega, o le tele (65%) o le cell i le NAC na faʻaalia ai le faʻaaogaina e taui eseese faalenatura (meaʻai ma vai), e tusa lava pe sili atu le palasi (sucrose) (Roop et al., 2002).

O nisi itu atonu na saofagā i le vavalalata ma faʻamaumauga oi ai nei. Muamua, na faʻaaogaina auala faʻapitoa faʻapitoa e suʻesuʻe ai galuega faʻavaomalo. O suʻesuʻega nei o loʻo faʻaogaina ai se metotia faʻasolosolo mo le siakiina o le faʻafouina o le faʻafouina o le namu e ala i ni faʻasolosolo eseese e lua e ala i le faʻaaogaina o le immunocytochemisty e lua mo Fos ma pERK, e mafai ai ona suʻesuʻeina le faʻamalosia o se tasi i le tele o vaega ole mafaufau. I le eseesega, o suʻesuʻega na faia e Carelli ma tagata faigaluega na faʻaaogaina le faʻaupuina o le electrophysiological faʻatapulaʻaina i le NAC o le faʻaleleia o meaola e faʻatautaia ai pe o le puleaina e le tagata lava ia o fualaau faʻasaina e faʻaaogaina ai le eletise e tasi o loʻo faʻaaogaina e taui masani.

Lona lua, o suʻesuʻega o loʻo iai i le taimi nei na suʻeina ai se eseesega masani faalenatura e pei o amioga tau feusuaʻiga e faatusatusa i suʻesuʻega muamua, lea na faʻaaogaina ai meaai ma vai i tama taala (Carelli, 2000). O meaai ma vai e sili atu le taua nai lo le paaga. O amioga tau feusuaiga e sili ona tauia ma o fusi na vave saunia CPP e faʻataʻitaʻiina (Agmo ma Berenfeld, 1990, Martinez ma Paredes, 2001, Tenk, 2008). E ui lava, o fuainumera taumafa e faʻatapulaʻaina ai le gaosia o CPP mo vai (Agmo et al., 1993, Perks ma Clifton, 1997) ma meaai (Perks ma Clifton, 1997), iO kuluga le faʻamaonia e sili ona lelei ma faʻaaogaina le CPP mo meaai e sili atu ona pala (Jarosz et al., 2006, Jarosz et al., 2007).

Tolu, o a matou suʻesuʻega e aofia ai vailaʻau eseese o le faʻaleagaina faʻatusatusa i suʻesuʻega muamua, faʻaaogaina methamphetamine ma amphetamine nai lo cocaine. O loʻo i ai i le taimi nei, o le Meth, ma i le amphetamine itiiti lava, na mafua ai le faʻamalosia o neurons e faʻamalosia foi i amioga tau feusuaʻiga. O aafiaga o fualaau oona atonu na avea foi ma vaega o mea na maua. O suʻesuʻega o loʻo i ai nei na faʻaaogaina ai manu na masani ona maua i feusuaiga, ae o fualaau faasaina. I le eseesega, o suʻesuʻega a le electrophysiological a Carelli ma tagata faigaluega e faʻaaogaina manu "lelei-aoaoina" lea na maua ai faʻamatalaga i cocaine.

O le mea lea, e mafai ona faʻaaogaina le Meth-faʻaaogaina o neurons e faʻaaogaina e amioga tau feusuaiga, ua suia i fualaau o fualaau oona. Ae ui i lea, o suʻesuʻega amata mai la matou galuega o loʻo fautua mai ai o le faʻamalositisi e ono le avea ma se mea sili ona taua e pei o amioga feusuaʻi ma togafitiga Meth i tamaʻitaʻi na togafitia faʻatasi ma Meth faʻatasi tutusa tutusa o vailaʻau faʻamalosi e pei ona lipotia i le suʻesuʻega o loʻo iai nei (20.3 ± 2.5% i le NAc ma le 27.8 ± 1.3% i le NAc shell, Frohmader ma Coolen, faʻamatalaga e lei lolomiina).

Ma le mea mulimuli, o suʻesuʻega o loʻo i ai nei na suʻesuʻeina le "tuusaʻo" o fualaau oona e faʻaaoga ai le faʻaaogaina o le pulega. O le mea lea, o le suʻesuʻega o loʻo iai nei e le faʻaalia mai ai faʻamatalaga e uiga i siosiomaga o loʻo i totonu o faʻamatalaga o fualaau faasaina poʻo faʻamatalaga e fesootaʻi ma le tau o fualaau oona, ae e faʻaalia ai le gaioiga o gaioiga e mafua mai i le gaioiga faʻataʻitaʻi o le vailaʻau. I suʻesuʻega o le electrophysiological muamua, o le mea na tupu i totonu o le sekone o tali faʻamalosia e le o se taunuuga o le gaioiga o le cocaine, ae e faalagolago tele i tulaga faʻapitoa i totonu o le faʻafoega o le puleaina o le tagata lava ia (Carelli, 2000, Carelli, 2002). Aemaise lava, o le gaioiga o le NAC e aʻafia i tali-tutoʻatasi faʻaalia o fua ninii e fesootaʻi atu ma le faʻamaʻiina o le koko faʻatasi ai ma le faʻaaogaina o meaʻai (ie, leve press pressing) i totonu o lenei faʻalapotopotoga amio (Carelli, 2000, Carelli ma Iames, 2001, Carelli, 2002, Carelli ma Wightman, 2004). I le aotelega, oa tatou sailiga o le faʻamalosia e ala i le natura ma le fualaau oona e mafai ona faʻamaonia mo le faʻamalosia e amioga faʻafeusuaiga ma pulea Meth ma Amph.

Meth ma feusuaiga e faʻaaogaina le faitau aofaʻi o neurons i totonu o le NAc core ma le atigi i se fua-faalagolago. O le kulupu o loʻo galulue i le NAC e mafai ona faʻatalanoa aafiaga o Meth i luga o le faʻamalosia ma le tauia o meatotino o amioga feusuaʻi pei o faʻasologa o le NAc e faʻaleagaina amioga tau feusuaiga (Liu et al., 1998, Kippin et al., 2004). E le gata i lea, o nei uaua e mafai ona avea ma nofoaga mo fualaau o fualaau e faalagolago i fualaau oona, talu mai le laʻititi o le Meth (1 mg / kg) na faʻaitiitia ai le numera o lua lua ua faʻamaonia i le 50% pe a faʻatusatusa i le maualuga o le Meth (4 mg / kg). E ui lava o lenei suʻesuʻega e le o faʻamalamalamaina le vailaʻau o le vailaʻau faʻasolosolo, o suʻesuʻega talu ai na faʻaalia ai le PERK ma le Fos expression i le NAC e faalagolago i dopamine (DA) ma le kulutamate receptors (Valjent et al., 2000, Ferguson et al., 2003, Valjent et al., 2005, Sun et al., 2008). E ui ina e le o manino pe afai o loʻo faʻalagolago le faʻalaʻiina o le neural activation i le NAc i luga o nei faʻaleleia, ua faʻaalia lenei mea i luga o isi vaega o le faiai, aemaise i le medial preoptic area (Lumley ma Hull, 1999, Dominguez et al., 2007). Ttane, Meth e mafai ona galue i luga o neurons e faʻaalia foi i le taimi o amioga feusuai e ala i le faʻaosoina o le dopamine ma le kulutamate receptors. O le matafaioi o le NAc glutamate i amioga tau feusuaʻiga e le o manino, ae ua maeʻa ona faʻamautuina e taua tele e le ATA le faʻamalosia o amioga tau feusuaiga. (Hull et al., 2002, Hull et al., 2004, Pfaus, 2009). O suʻesuʻega ole microdialysis na lipotia mai ai le faateleina o le NAc DA efflux ao faagasolo taimi masani ma faʻataʻitaʻiga o amioga tau feusuaiga a alii (Fiorino ma Phillips, 1999a, Lorrain et al., 1999) ma le mesolimbic DA efflux ua faʻasaʻoina i le faʻamalosia o le amataina ma le tausiga o amioga feusuaʻiga i le rat (Pfaus ma Everitt, 1995). E le gata i lea, o faʻataʻitaʻiga faʻataʻitaʻiga a le ATA o loʻo faʻaalia ai le osofaʻiga a le ATA i le NAC ia amioga tau feusuaiga, ae o le agonists e faafaigofie ai le amataina o amioga tau feusuaigar (Everitt et al., 1989, Pfaus ma Phillips, 1989). O le mea lea, e mafai e Meth ona aʻafia ai le faʻamalosiaga mo amioga tau feusuaiga e ala i le faʻatoagaina mai o faʻamaumauga ACC.

I le faatusatusa atu i le NAc, o le fuainumera o luasele lua ua faailogaina i totonu o le BLA ma le ACA na tumau pea le le suia e tusa lava po o le a le Meth. O le BLA e taua tele mo aʻoaʻoga vavalalata faʻatasi ma e matua aʻafia i le faʻalagolago i le faʻalagolago ma le tauia o tau i le taimi o le tali atu i meafaigaluega (Everitt et al., 1999, Cardinal et al., 2002, Vaʻai, 2002). BLA laumei faʻasalalau faʻaalia le faʻaitiitia o le mamafa o le levela mo tuʻusaʻoga faʻapitoa e fetaui ma meaai (Everitt et al., 1989) poʻo le faʻamalosia o feusuaiga (Everitt et al., 1989, Everitt, 1990). I le eseesega, o lenei faiga e le afaina ai le vaega taua o le fafagaina ma amioga tau feusuaiga (Cardinal et al., 2002). O le BLA o loʻo taʻalo foi i se vaega autu i le manatuaina o fualaau faʻapitoa e aʻafia i fualaau faʻasaina (Grace ma Rosenkranz, 2002, Laviolette ma Grace, 2006). Liona po o le faʻaaogaina o vailaau faʻamalosia o le BLA poloka le mauaina (Whitelaw et al., 1996) ma faʻamatalaga (Grimm ma See, 2000) toe faʻaleleia le koko o cocaine, ae le aʻafia ai le faʻagasologa o le faʻaaogaina o fualaau. Ma le isi, Ua faʻafesoʻotaʻi saʻo Amph i totonu o faʻamaumauga a le BLA i se toe faʻaleleia o fualaau faʻasaina i le i ai o faʻamaumauga (Tagaʻi ma al., 2003). O le mea lea, e mafai e le psychostimulant-faʻaleleia atili le faʻasalalauga a le AT i totonu o le BLA iʻuga o lagona faʻalagona ma le sailia (Ledford et al., 2003) o le tau feusuaʻiga, ma o lea ua saofagā ai i le faʻaleleia atili o feusuaʻiga tau feusuaʻiga ma le manaʻoga na lipotia mai e le aufaitaʻaga Meth (Semple et al., 2002, Green ma Halkitis, 2006).

I le ACA, o le faʻafouina o le faʻaaogaina o le faʻaaogaina o le faʻaaogaina o fuainumera e faʻaaogaina ai feusuaʻiga, o le faʻavae-tutoʻatasi ma patino mo Meth, talu ai e lei matauina ma Amph. E ui o loʻo i ai Meth ma Amph faʻaputu ma faʻavae o mea tau vailaʻau, o Meth o se tagata e sili atu le malosi o lona mafaufau nai lo Amph ma le umi o ona aʻafiaga (NIDA, 2006). Studies by Goodwin et al. na faʻaalia ai e Meth se galulolo sili atu ma faʻalavelaveina le faʻatagaina o le faʻaaogaina o le TA i le kenele NAc nai lo Amph. O nei uiga e ono mafai ona fesoasoani i mea tau vaisu o Meth faʻatusatusa ia Amph (Goodwin et al., 2009) ma masalo o vaʻaia o le faʻafouina o le neural e matauina i le va o fualaau e lua. E ui i lea, e leʻo manino pe o mamanu eseese o taunuʻuga ona o le eseesega o feeseeseaiga i le va o fualaau oona poʻo le malosi o mataupu e fesoʻotaʻi ma atotoʻo o loʻo faʻafaigaluegaina ma isi suʻesuʻega e manaʻomia.

O le faʻaosoosoina e Meth ma feusuaiga e le o matauina i isi sousregiona o le mPFC (IL ma le PL). I le rat, o le ACA na suʻesuʻeina lautele e ala i le faʻaaogaina o galuega faʻapitoa, lagolagoina o se matafaioi i faʻalapotopotoga faʻamalosia-faʻamalosia (Everitt et al., 1999, Vaʻai, 2002, Cardinal et al., 2003). O loʻo i ai le tele o faʻamaoniga e aofia ai le mPFC i fualaau oona ma toe faʻafoʻi atu i fualaau faʻatau fualaau ma fualaau faʻatau fua i tama ma tama (Grant et al., 1996, Childress et al., 1999, Capriles et al., 2003, McLaughlin ma See, 2003, Shaham et al., 2003, Kalivas ma Volkow, 2005). O aʻulaina ma lenei, na folasia ai o le mPFC e mafua ona o le masani ona faʻaalia i fualaau o le faʻaleagaina e ono aʻafia mo le faʻaitiitia o le malosi o le manaʻoga ma le faʻateleina o amio pulea e pei ona matauina i le tele o mea ua fai ma vaisu (Jentsch ma Taylor, 1999). O faʻamatalaga lata mai mai la matou fale suesue na faʻaalia ai le mafuaʻaga o le mPFC i le faʻaauau pea ona sailia amioga tau feusuaʻiga pe a fesootaʻi atu i se mea faʻaosofia (Davis et al., 2003). E ui lava e leʻi suʻesuʻeina e lenei suʻesuʻega le ACA, ae lagolagoina le manatu e faapea, o le MPFC (ma le ACA) e faʻasalalau aafiaga o Meth i le leiloa o le pulea o le amio pulea e pei ona lipotia mai e le au Meth abusers (Salo et al., 2007).

I le faʻasalaga, o nei suʻesuʻega e faia ai se laasaga taua e agai atu i se malamalamaga sili atu i le faʻaaogaina o fualaau faʻasaina i luga o auala i totonu o le ala lea e masani ona vavalalata taui faalenatura. E le gata i lea, o nei suʻesuʻega ua faʻamaonia ai e ese mai i le talitonuga o loʻo iai nei fualaau faasaina o le faʻaleagaina e le faʻamalosia ai ia lava sene i totonu o le mesolimbic system e avea ma taui masani, Meth, ma i se tulaga maualalo Amph, faʻagaoioia ia lava filifili e pei o amio feusuaʻi. I le isi itu, o nei tagata o loʻo galulue faʻatasi i le fogaeleele e ono aʻafia ai le sailia o taui masani pe a uma ona faʻamaʻi fualaau. Ma le mea mulimuli, o taunuʻuga o lenei suʻesuʻega e ono fesoasoani tele i lo tatou malamalama i le faavae o mea ua fai ma vaisu lautele. O faʻatusatusaga o mea e talitutusa ma eseesega, faʻapea foʻi suiga i le faʻafouina o le tino o le manolimbic e mafua mai i feusuaiga faʻafeusuaiga ma fualaau faʻaleagaina e mafai ona taʻitaʻia atili ai le malamalama i le faʻaaogaina o fualaau faʻasaina ma suiga faʻaletausaga i taui masani.

tautinoga

O lenei suʻesuʻega na lagolagoina e fesoasoani mai National Institute of Health Health R01 DA014591 ma le Canadian Institute of Health Research RN 014705 i LMC.

FUAFUAGA

  • ABC
  • avidin-biotin-horseradish peroxyidase complex
  • ACA
  • tuatusi pito i luma
  • Amene
  • d-amphetamine
  • BLA
  • amygdala faʻatau
  • BNSTpl
  • pito i luga ole pito i luga ole pito i tua o le pito i lalo
  • BNSTpm
  • Tuʻu i luga o le moega mo le moega o le laina
  • BT
  • biotinylated tyramide
  • CeA
  • centy amygdala
  • CPP
  • nofoaga e iai le mea e manaʻo iai
  • E
  • ejaculation
  • EL
  • feusuaiga ejaculation
  • IF
  • infameimbic area
  • IL
  • taofiofia faʻalavelave
  • IM
  • faʻasalaga
  • M
  • mauga
  • MAP Kinase
  • mitogen-activated protein kinase
  • MEApd
  • postrodorsal medial amygdala
  • Meth
  • methamphetamine
  • ML
  • mauga tautau
  • mPFC
  • medial frontfront cortex
  • MPN
  • vailaau faʻasolosolo
  • NAc
  • nucleus Accumbens
  • PB
  • fusi phosphate
  • PBS
  • phosphate fagu masima
  • PEI
  • Post ejaculatory interval
  • PERK
  • PhoP Kinase phosphorylated
  • PL
  • vaega amata
  • VTA
  • vaega faʻalautele faʻalautele

Faamatalaga Faʻamatalaga

Le Faʻalauiloa a le Lomitusi: O le PDF lenei o se tusitusiga e leʻi faʻaaogaina lea na taliaina mo le lolomiina. I le avea ai ma se tautua mo o tatou tagata faʻatau, o loʻo tatou saunia lenei uluai kopi o tusitusiga. O le tusitusiga o le a faʻaaogaina le kopiina, faʻavasegaina, ma le toe iloiloga o le faʻamaoniga ao leʻi faʻasalalauina i lona tulaga mulimuli. Faamolemole ia matau i le faagasologa o le gaosiga e mafai ona maua ai mea sese e mafai ona aafia ai le anotusi, ma o tulafono uma e le faatagaina e faatatau i le tusi o talaaga.

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