Hana ka Methamphetamine ma nā kaʻina o nā neurones e hoʻomalu ana i ka moekolohe i nā kāne kāne (2010)

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

ʻO Frohmader KS, Makaika J, RAʻike, Lehman MN, Coolen LM.

kahi

Keʻena o ka Anatomy a me ka Cell Biology, Ke Kulanui o Medicine a me ke Kauka, Ke Kulanui o Western Ontario, Lākana, ON, Kanada, N6A 5C1.

Hōʻuluʻulu Manaʻo

ʻO ka Methamphetamine (Meth) he mea hoʻonāukiuki nui loa. Hoʻopiliʻia ka hana hoʻomāʻewaʻewa Meth me ka hana o ka moe kolohe moe kolohe a me ka piʻiʻana o ka palekana o nā Immunodeficiency Virus a me nā mea hoʻohana Meth e hoʻonui i ka moekolohe, ka huhū, a me ka leʻaleʻa. ʻAʻoheʻike i kahi kumu olaola no kēia mea hoʻohana i ka lāʻauʻauana. Ke hōʻike nei kaʻike i kēia manawaʻo ka lawelaweʻana o Meth ma nāʻiole kāne kāne e hana i nā neurons ma nāʻaoʻao lolo o ka pūnaha mesolimbic i komo i ka hoʻoponoponoʻana i ka moe kolohe. ʻO ke kiko'ī, nā Meth a me ke kelehele e hoʻopaʻa i nā pūnaewele i loko o ka piko a me ka shell shell accumbens, amygdala basolateral, a me ka cortex cingular mua. Hōʻike kēia mauʻike ma ka hoʻohālikelike i nā lāʻau lapaʻau o ka hana hoʻomāinoino i kēia manawa e hiki ke hoʻoikaika i nā pū like like me ka mea hoʻonāʻano maoli,ʻo ia ka moekolohe, a ma ka hopena e hoʻoikaika i ka noi ikaika no kēia uku kūlohelohe.

Keywords: ka nucleus accumbens, amygdala paʻakikī, kino kinai mua, hoʻohana lāʻau, hōʻailona, ​​hōʻailona

Hoʻoponoponoʻia ka hoʻouluʻana a me ka uku e ka mesolimbic pūnaewele, kahi pūnaewele pūnaewele o nā wahi lolo e komo ana i ka'āpana kaʻina (VTA) nucleus accumbens (NAc), amygdala basolateral, a me ka cortex medial prefrontal (mPFC) (Kelley, 2004, ʻO Kalivas a me Volkow, 2005). Aia kekahi hōʻike kūpono e hoʻoukaʻia ka pūnaha mesolimbic ma ka paneʻana i nā mea likeʻole o ka hōʻino (ʻO Di Chiara a me Imperato, 1988, ʻO Chang et al., 1997, Ranaldi et al., 1999) a no ka hana maʻamau i nā hana e like me ka moe kolohe (Fiorino et al., 1997, Balfour et al., 2004). ʻO ka moekolohe kāne kāne, a me keʻano ejaculation, he uku nui a hoʻonuiʻia i nāʻano holoholona (Pfaus et al., 2001). Hiki i nā koʻi'ōpiopio ke hana i kahi koho kūpono (CPP) no ke kāwili (Agmo a me Berenfeld, 1990, Martinez a me Paredes, 2001, Tenk, 2008), a e hana i nā hana hana e hiki ai ke komo i nā wāhine hānai wahine (Everitt et al., 1987, Pūʻokoʻa a me Stacey, 1987). Hoʻoikaika a hoʻouluhuaʻia ka lāʻau lapaʻau, aʻo nā holoholona e aʻo i ka hoʻohana ponoʻana i nā mea hanaʻino, e like me nā opiates, nā nicotine, ka waiʻona, a me nā psychostimulants (Pōʻaka, 1996, Pierce a me Andresan, 2006, Feltenstein a me See, 2008). ʻOiai uaʻikeʻiaʻo nā lāʻau lapaʻau a me ka hana kolohe e hoʻonāuki i nā mahele mesolimbic, i kēia manawaʻaʻole maopopo i ka hoʻohanaʻiaʻana o nā neurons e like me ka lāʻau lapaʻau e pili ana i ka moe kolohe.

Ua hōʻike nā kohopili kohopili i ka hanaʻana o kaʻai a me ka cocaine i nā neurons ma ka NAC. Eia naʻe,ʻaʻole e hoʻouka nā mea hoʻoikaikaʻelua i nā pūnaewele like i loko o ka NAc (Kulanui a me., 2000, Kulanui a me Wondolowski, 2003). Eia kekahi,ʻo kaʻai a me ka hoʻopiliʻana i ka hoʻoponoponoʻana iā ia iho,ʻaʻole ia e hoʻololi i nā hoʻololiʻana o nā pono o ka pono o ka pono i nā mea iʻikeʻia e ka cocaine (Chen et al., 2008). I ka hoʻohālikeʻana,ʻo ka hōʻiliʻiliʻana o nā hōʻike e hōʻike ana i ka hana maʻamau male kāne a me nā lāʻau lapaʻau e hana maoli ma nāʻehu mesolimbic like. ʻO nā Psychostimulants a me nā opioids e hoʻololi i ka'ōlelo o ka moe kolohe ma nāʻiole kāne kāne (Mitchell a me Stewart, 1990, Fiorino a me Phillips, 1999a, Fiorino a me Phillips, 1999b). Hōʻike houʻia nāʻikepili hou mai kā mākou papahana i ka hana pilina e hoʻololi i ka paneʻana i nā psychostimulants e like me kaʻikeʻana o nā pane locomotorʻano nui a me kaʻike i loaʻa i ka amphetamine ma nā holoholona kolohe (Pitchers et al., 2009). Ua mālama muaʻia kekahiʻano likeʻole me kaʻike pinepineʻiaʻana i ka amphetamine a iʻole nā ​​lāʻau lapaʻauʻino (Lett, 1989, Shippenberg a me Heidbreder, 1995, Shippenberg et al., 1996, Vanderschuren lāuaʻo Kalivas, 2000). ʻO kēia mau hopena, hōʻikeʻia nā hana maʻamau a me nā pane i ka lāʻau hoʻomāinoino i nā mea e like me nā mea likeʻole ma ka pūnaha mesolimbic. No laila, o ka pahuhopu mua o ka papahana o kēia manawa,ʻo ia ka nānāʻana i ka hoʻopiliʻana i ka hanuʻana o ka pūnaha mesolimbic ma muli o ka moe kolohe a me ka hoʻoponopono lāʻau hōʻailona ma ka holoholona like. Ma keʻano, ua ho'āʻo mākou i ke kuhiakau e hana ana ka psychostimulant, methamphetamine (Meth) i nā neu e like me ka mea maʻamau i ka moe kolohe.

ʻO Meth kekahi o nā lāʻau lapaʻau i hōʻino loaʻia ma ka Honua (NIDA, 2006, Ellkashef et al., 2008) aa ua pili pinepine ia i ka halihali kolohe. ʻO ka mea e mahalo ai, hōʻike ka poʻe Meth i ka hoʻonākino a me ke aloha, a me ka leʻaleʻa maikaʻi o ka wahine (Semple et al., 2002, Schilder et al., 2005). Eia kekahi, Hoʻopiliʻia ka hana hoʻomāʻewaʻewa Meth me ka hana kolohe (Rawson et al., 2002). Hōʻike pinepine ka poʻe hoʻolaha i ka nui o nā hoa pili i ka moekolohe aʻaʻole hiki ke hoʻohana i ka palekana ma mua o nā mea hana lāʻau lāʻau'ē aʻe (Somlai et al., 2003, Springer et al., 2007). ʻO ka mea pōʻino,ʻo nā haʻawina e hōʻike ana iā Meth e hoʻohana anaʻo ia he wānana i ka hoʻoweliweli i ka moe kolohe, ua kaupalenaʻia ma muli o ka hilinaʻiʻana i nā hōʻike pilikino iʻole i hōʻoiaʻia (Elifson et al., 2006). No laila,ʻo ka hoʻokolokoloʻana i loko o ka pūnaewele pūnaewele o nā hoʻololi Meth-i hoʻokomoʻia i ka moekolohe i loko o nāʻano holoholona e koiʻia no ka hoʻomaopopoʻana i kēia kamepiula hōʻailona.

Ma ka nānāʻana i nā hōʻike i hōʻikeʻia i luna nei e hōʻike ana i nā lāʻau lapaʻau, a me Meth paha, hiki ke hana i nā neu i pili i kaʻimiʻana i ka moe kolohe,ʻo ka pahuhopu o ka papahana o kēia manawaʻo ia e nānā i ka hoʻonā i ke kino ma ka moekolohe a me ka hoʻoponoponoʻana o ka Methcromalnt Meth. Ua hoʻohanaʻia kēia hana i kahiʻano neuroanatics, e hoʻohana ana i nāʻano immunohistochical i nā kinona mua loa Fos a Pho phosphorylated Map Kinase (pERK) no kaʻikeʻana i ka hoʻoikaikaʻana o ka neural ma muli o ka moekolohe me Meth. Hōʻikeʻia ka Fos i loko o ka pūpū o nā pūnaewele, me ka paukū'ōlelo kiʻekiʻe 30-90 mau minuke ma hope o ka hoʻonāʻana o ka neuron. He nui nā hōʻike e hoʻonāukiuki ka hopena o ka wahine ma ka lolo (Fos expression in the brain)ʻO Pfaus a me Heeb, 1997, ʻO kaʻike a me ka'ahuʻula, 1998), me ka pūnaewele mesocorticolimbic (Robertson et al., 1991, Balfour et al., 2004). Aia kekahi mauʻike e hiki i nā lāʻau lapaʻau hoʻomāinoino ke hoʻopili i ka'ōlelo ma loko o ka pūnaehana mesocorticolimbic (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005). I ka hoʻohālikeʻana i ka'ōlelo o Fos, phosphorylation o ERK he mea ikaika loa ia a ke hanaʻia nei he mau minuke 5-20 wale nō ma hope o ka hoʻoukaʻana o ka neuronal. Nāʻike kūlohelohe kūlohelohe o Fos a me PERK e hoʻolilo iā lākou i mea hoʻolālā maikaʻi no ka hoʻouluʻana o nā neuronal hou e nā kumu hoʻoikaikaʻelua.

NĀ KUMU HOPE

Nā Kaupapa

ʻO nā keiki kāne Sprague Dawley (210-225 g) kāne nui i loaʻa mai mai nā Laboratoriesʻo Charles River (Montreal, QC, Canada) i hoʻopaʻaʻiaʻelua ma kēlā pahu i loko o nā plexiglas maʻamau (home cages). Ua mālamaʻia ka lumi holoholona ma kahi 12 / 12 h i hoʻohuli i ke kukui (kukui i 10.00 h). Loaʻa nā meaʻai a me nā wai ad libitum. Ua hanaʻia nā ho'āʻoʻana i ka hapalua mua o ka pōʻeleʻele ma lalo o ka mālamalama uila. Hanaʻia nā wāhine i ka hoʻohanaʻia no ka moekoloheʻana i ka mea i hoʻohuiʻia ma lalo o ka hohonu anestheia (13 mg / kg ketamine a me 87 mg / kg xylazine) a loaʻa kahi'āpana subcutaneous i loaʻa me ka 5% estradiol benzoate (EB) a me ka 95% cholesterol. Ua hoʻokomoʻia ka laweʻana o ka wahine ma ke subcutaneous (sc) e hoʻomalu i ka 500 μg progesterone ma ka 0.1 ml manamele sesame 4 h ma mua o ka hoʻokolohuaʻana. Ua'āponoʻia nā papa hana a pau e ke Kula Kahu Ola ma ke Kulanui o Western Ontario a e like me nā kuhikuhi i hōʻikeʻia e ka Kōmike Kanai no nā Hana Lima.

Hōʻike Hōʻike

Hōʻikeʻo 1 a me 2: Uaʻaeʻia nāʻiole kāne (n = 37) e male me kahi wahine hānai i kahi ejaculation (E) aiʻole no 30 min, i hele mua ma nā pahu uila hoʻomaʻemaʻe (60 × 45 × 50 cm) i loko oʻelima manawa nā manawa hoʻolālā mua-hōʻoia, e loaʻa ai kaʻike pilina. I loko o nā kau hopeʻelua, ua hoʻopaʻaʻia nā pae hiʻona maʻamau no ka hana maʻamau, e like me: ke kaheʻana o ka mauna (ML, ka manawa mai ka hoʻokomoʻana i ka wahine a hiki i ka mauna mua), ka moe hoʻomaha (IL, ka manawa mai ka hoʻokomoʻana i ka wahine a hiki i ka mauna mua ke komoʻana i kahi o ka hoʻoukaʻana), ka hope o ka hoʻolālā (EL, ka manawa mai ka hopena i ka hoʻokuʻu muaʻana), ka helu o nā kau (M), a me ka helu o nā hoʻoweliweli (IM) (Agmo, 1997). Loaʻa i nā kāne a pau ka 1 ml / kg i kēlā lā i kēia lā o ka nininiʻana i ka 0.9% NaCl (saline; sc) 3 mau lā ma mua o ka lā hoʻokoehua, no ka maʻamau i ka lawelaweʻana a me ke kaʻina. I kekahi lā ma mua o ka lā hōʻoia, ua noho nā kāne kāne a pau. Ma nā kāne kūpono, hiki ke hoʻokomoʻia nā Fos ma nāʻikepili pilikino i pili i ka pilina mua mua (ʻO Balfour et al, 2004). No laila,ʻo nā mea maʻamau a me ka mana i nā hopena hope loa i mālamaʻia i loko o ka hale home (eʻae i ka nānāʻana i nāʻike kūlana) no ka paleʻana i ka hoʻouluʻana i ka conditioned-cue i nā kāne ma waho. Ua hoʻokaʻawaleʻia nā kāne i nā hui hoʻokolohuaʻewalu iʻaʻaʻole i kekahiʻano o ka hana maʻamau i loko o nā kau hopeʻelua (ʻikeʻole i hōʻikeʻia). I ka hoʻokolokolo hope loa, uaʻaeʻia nā kāne e male ma ka hale o lākou a hiki i ka manawa e hōʻike ai i ka male (male) aʻaʻole i loaʻa i ka hoa wahine (ka wahineʻole). Hoʻopiliʻia nā kāne male a pau i ka 60 mau minuke ma hope o ka hoʻomakaʻana o ka maleʻana eʻae ai e hoʻowākino i ka hōʻike Fos-induced. Loaʻa i nā kāne he inikua o 4 mg / kg Meth a iʻole 1 ml / kg saline (sc) (n = 4), 10 (hoʻokolohua 1) a iʻole 15 (hoʻokolohua 2) min ma mua o kaʻailaʻana, no ka hōʻoiaʻana i ka phosphorylation i hoʻokomoʻia i ka lāʻau o MAP kinase. ʻO nā hana a me ka manawa ma mua o ka hoʻonoeʻana i hoʻokumuʻia ma nā hōʻike mua (Choe et al., 2002, ʻO Choe a me Wang, 2002, Chen a me Chen, 2004, Mizoguchi et al., 2004, Ishikawa et al., 2006). Manaʻo nā papa hana ma nā kāne i kūʻole, akā loaʻa iā Meth 10 (n = 7) aiʻole 15 (n = 5) minu ma mua o ka mōhai, a iʻole nā ​​mea heniki 10 (n = 5) aiʻole 15 (n = 4) minu ma mua o ka mōhai . Ma hope o ka mōhai, ua hanaʻia nā noʻonoʻo no ka immunohistochemistry.

Hōʻike 3: Ma muli o ka hoʻohanaʻana o ka meth kiʻekiʻe o ka hoʻokolohua 1 a me ka 2, ua hanaʻia kekahi hoʻolālā neuroanatomi'ē aʻe no kaʻikeʻana i ka hana maʻamau a me ka hopena haʻahaʻa o Meth e hoʻohuli i nā hilinaʻi hopena no ka hoʻouluʻana i ke neural activation. Ua hanaʻia kēia hana ma kahiʻano like me nā hoʻokolohua 1 a me 2. Eia nō naʻe, ma ka hōʻoia hope loa, ua loaʻa i nā huiʻeleʻele a me ka huiʻole (n = 6) nā 1 mg / kg Meth (sc) 15 min ma mua o ka mōhai.

Hoʻokolohua 4: No ka ho'āʻoʻana inā hoʻololiʻia keʻano o ka wahine a me Meth no Meth, uaʻikeʻia kēia hoʻokolohua inā paha eʻikeʻia ana nāʻano likeʻole o ka hoʻouluʻana i nā neural activity me ka amphetamine psyphostimulant (Amph). Ua hanaʻia kēia hoʻokolohua ma kahiʻano like me nā hoʻokolohua 1 a me 2. Eia naʻe, ma ka ho'āʻo hope, ua lawelaweʻia nā kāne male Amph (5 mg / kg) aiʻole saline (1 mg / kg) (sc) 15 min ma mua o ka mōhai (n = 5 kēlā me kēia). Ua mālama nā kāne mālamaʻole i ka saline a iʻole nā ​​Amph 15 minuke ma mua o ka mōhai. ʻO kahi o nā hiʻohiʻona hoʻokolohua i hoʻohanaʻia ma nā hoʻokolohua 1-4 i hoʻolakoʻia 1 Pūnaewele.

1 Pūnaewele      

ʻO nā hiʻohiʻona o nā hui hoʻokolohua i loko o nā hoʻokolohua 1-4.

Ka hoʻomākaukau hoʻomākaukauʻana

Hoʻopiliʻia nā holoholona me ka pentobarbital (270 mg / kg; ip) a hoʻokuʻuʻia me ka 5 ml o saline i ukaliʻia e 500 ml 4% paraformaldehyde ma ka XWUMX M phosphate buffer (PB). Ua hoʻokuʻuʻia nā umauma a hoʻonohonohoʻia no ka 0.1 h ma ke ana wela ma ka mea like, a laila ua bapetizoʻia i ka 1% sucrose a me ka 20% Sodium Azide ma 0.01 M PB a mālamaʻia ma 0.1 ° C. Ua kāʻiliʻia nā māhele o ka Coronal (4 μm) i kahi mīkini mikena (H35R, Micron, Kelemānia), i hōʻiliʻiliʻia i nā hananaʻehā e like me ka solution cryoprotectant (400% sucrose a me 30% ethylene glycol ma 30 M PB) a mālamaʻia ma 0.1 C C hoʻoponopono.

Immunohistochemistry

Hoʻokumuʻia nā hāʻina a pau ma kahi pāmahana o ke keʻena a me kaʻoluʻolu haʻahaʻa. Ua holoi nuiʻia nā papa'āina māmā me ka 0.1 M Phosphate-buferfered saline (PBS) ma waena o nā'ākuhi. Hoʻopukaʻia nā lālā ma 1% H2O2 no 10 min, a laila ua kāpenaʻia i loko o ka hoʻopiʻi hoʻopunipuni (PBS pūnaewele 0.1% bovine a me 0.4% Triton X-100) no 1 h.

PERK / Fos

Hoʻokumuʻia ka iwi i ka pō me ka'āpana polyplonal rabbit e kū'ē i ka p42 a me ka p44 palapala kinases ERK1 a me ka ERK2 (pERK; 1: Hōʻoia 400 hōʻike 1 19; 1: 4.000 hoʻokolohua 2 a me ka 3 pūnaewele 21; 9101 H hui pū me ka mea me ka biobolic agonomic IgG (1: 1; Jackson Immunoresearch Laboratories, West Grove, PA) a me ka complexed avidin-horseradish peroxyidase (ABC Elite; 500: 1, Vector Laboratories, Burlingame, CA). A laila, ua hoʻopiʻiʻia ke kikowaena no ka 1000 min me ka tytemide biotinylated (BT; 10: 1 i PBS + 250% H2O2; Ka hōʻailona hōʻailona hōʻailona, ​​NEN Life Sciences, Boston, MA) a no ka 30 me Alexa 488 strepavidin conjugated (1: 100, Jackson Immunoresearch Laboratories, West Grove, PA). ʻO ka hope aʻe, ua hoʻopiʻiʻia kaʻiʻo i ka pō me ka'āpana polyclonal rabbit e pili ana i ka C-Fos (1: 500; SC-52;ʻo Santa Cruz Biotechnology, Santa Cruz, CA), a ma muli o ka hoʻopunipuni 30 min me ka'opi pōpilikia Alexa 555 (1: 200; Jackson Nā Kūkākūkā Hōʻoia Kū'ē, West Grove, PA). Ma hope o kaʻokiʻana, ua holoiʻia nā paukū ma 0.1 M PB, hoʻokumuʻia i nā kiʻi slide me 0.3% gelatin ma ddH20 a kāpiliʻia me kahi mea kani (Gelvatol) i loko o ka mea anti-Flying agent 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). ʻO nā mana o ka Immunohistochimalikoa ka hanaʻole o kekahi a me nā'aleoho muaʻelua, e puka ana i ka nele o ka lakaʻana ma ka nalu kūpono.

KaʻIkepiliʻIkepili

Ka moe kolohe

No nā hoʻokolohuaʻehā a pau, ua kākauʻia nā palena maʻamau no ka hana pilina e like me ia i ho'ākākaʻia ma luna nei a ua hōʻoiaʻia ma o ka hoʻohanaʻana i ke kānana holoʻokoʻa (ANOVA). ʻO kaʻikepiliʻikepili o ka hana maʻamau i ka lā o ka lā hope loa hōʻikeʻole i nāʻokoʻa nui ma waena o nā hui ma kekahi o nā palena o ka hana maʻamau.

PERK / Fos Cell Counts

ʻO nā pūnaewele i hoʻopaʻaʻia no nā Fos a me ka PERK, heluʻia lākou i loko o ka papa caualal o ka NAc nui a me nā lalo lalo, amygdala kūpale (BLA), medial amygdala (MEApd), pokapū amygdala (CeA), medial preoptic nucleus (MPN), postromedial ka pūnana hope loa o ka stria terminalis (BNSTpm a me BNSTpl), a me ka'āpana o mua (ACA), prelimbic (PL), a me infregimbic (IL) mau lalo o ka mPFC. Ua kiʻiʻia nā kiʻi i kahi kamepiula CCD hauʻoli (Microfire, Optronics) i hoʻopaʻaʻia i kahi microscope Leica (DM500B, Leica Microsystems, Wetzlar, Kelemānia) a me ka polokalamu Neurolucida (MicroBrightfield Inc) me nā hoʻonohonoho hoʻohāmele hoʻonohonoho no nā kumuhana (e hoʻohana i nā manaʻo 10x). I ka hoʻohanaʻana i nā polokalamu neurolucida, ua hoʻonohonohoʻia nā māhele o ka hōʻuluʻuluʻana e pili ana i nā palena'āina (Swanson, 1998) he kūikawā no kēlā me kēia māhele lolo (ʻike Hōʻike 1). Ua hoʻohanaʻia nā māhele kūʻokoʻa o nā hoʻopiliʻana ma nā āpau a pau i koe kaʻole o ka palapala a me ka shell. Ma nāʻaoʻao hope loa,ʻaʻole i hui likeʻia ka PERK a me ka Fos ma nāʻano likeʻole. No laila, ua hoʻonohonohoʻia nā kumu a me nā shell a pau e pili ana i nā palena'āina (ka makani ventralle, nā mea āpau, a me nā mokupuni o Calleja). ʻAʻole i like nā mahele o ka hoʻokolohua ma waena o nā hui hoʻokolohua, a ua liloʻo 1.3 mm2 ma ka NAc kumu a me ka shell. ʻO nā kūlana kūʻokoʻa o ka hoʻopiliʻana no nā koena i koe: 1.6 mm2 i ka BLA, 2.5 a me ka 2.25 mm2 i loko o MEApd a me CeA, 1.0 mm2 i ka MPN, 1.25 mm2 i nā kaʻina BNST a me nā mPFC, a me 3.15 mm2 i ka VTA. ʻElua mau lālā i heluʻia no ka lolo i kēlā me kēia holoholona ma kēlā me kēia holoholona, ​​a me ka helu o nā pūnaewele i kāinoaʻia a me nā lua no PERK a me Fos a me nā hapa o nā pūnaehana PERK i ho'ākākaʻia i ka hōʻikeʻana o Fos marker. No nā ho'āʻoʻana o 1, 2, a me 4, ua hoʻohālikelikeʻia nā kauʻana o nā hui ma ke alaʻelua ANOVA (nā kumu: pili me ka lāʻau) a me ka LSD Fisher no mahope iho ke kūlike me kahi nui o ka 0.05. No ka hoʻokolohua 3, ua hoʻohālikelikeʻia nā kauʻana o nā hui me nā ho'āʻoʻole i hoʻolālāʻia ma kahiʻano nui o 0.05.

Hōʻike 1      

Nā kiʻi hoʻonohonoho a me nā kiʻi e hōʻike ana i nā mākau o ka hōʻailona. Hōʻikeʻia nā māhele hoʻolālāʻana i nā hiʻona'āina kūikawā no kēlā me kēia māhele lolo,ʻaʻole i like i waena o nā hui hoʻokolohua, aʻo 1.25 mm kēia2 i nā subregions mPFC (a), 1.3 mm2 i ka ...

Images

Nā kiʻi kiʻi kiʻi no Hōʻike 3 ua hopuʻia me ka kamera CCD (DFC 340FX, Leica) i pili i ka microscope Leica (DM500B) a ua laweʻia mai i loko o Adobe Photoshop 9.0 polokalamu (Adobe Systems, San Jose, CA). ʻAʻole i hoʻololiʻia nā kiʻi ma kekahiʻano'ē aʻe no ka hoʻoponoponoʻana o ka'ōlohi.

Hōʻike 3      

Hoʻolālāʻia nā kiʻi no nā lālā NAc no Fos (ʻula, a, g, j) a me pERK (green; b, e, h, k) o nā holoholona o kēlā me kēia hui hoʻokolohua:ʻAʻohe male + Sal (a, b, c) , Sex + Sal (d, e, f), No Sex + Meth (g, h, i), a me Sex + Meth (j, k, l). ʻO nā paneli'ākau ...

Nā Hua

ʻO ke kino o ke kino o ka'ōlēʻole ma o ka hanaʻino a me ka Meth Administration

Hōʻike 1:ʻO kaʻike o nā pūnaewele i kahaʻia a me nā lua i loaʻa i ka Meth 10 mau minuke ma mua o ka mōhai hōʻike i nā Fos i hoʻokomoʻia i loko o ka MPN, BNSTpm, NAc a me ka shell, BLA, VTA, a me nā kaʻina o lalo o ka mPFC, e like me nā haʻawina mua e hōʻike ana i nā'ōlelo i hoʻokomoʻia i loko o kēia mau wahi (ʻO Baum a me Everitt, 1992, ʻO Pfaus a me Heeb, 1997, ʻO kaʻike a me ka'ahuʻula, 1998, Hull et al., 1999). Hoʻoponopono Meth 10 mau minuke ma mua o ka mōhai i hoʻokomoʻia ma loko o ka NAc a me ka shell, BLA, MeApd, CeA, BNSTpl, a me nā māhele o mPFC, e like me nā papa hana i hoʻokomoʻia e kekahi poʻe psychostimulants (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005).

Eia kekahi, uaʻikeʻiaʻekolu mau hiʻohiʻona o ka hoʻohālikeʻana o ka neural i ka hana moekolohe a me Meth:ʻO ka mea mua, uaʻikeʻia nā wahi o ka lolo i kahi e hana ai ka wahine a me nā lāʻau i nā poʻe neural nonlap (2 Pūnaewele). ʻO ke kikoʻī, i ke CeA, MEApd, BNSTpl, a me mPFC, hoʻonui nui i nā pERK i hoʻokomo ʻia i ka lāʻau (F (1,16) = 7.39-48.8; p = 0.015- <0.001) a me Fos i hoʻokomo ʻia i ka moekolohe (F (1,16, 16.53) = 158.83-0.001; p <1,16) ʻike ʻia. Eia nō naʻe, i kēia mau ʻāina ʻaʻohe piʻi nui o nā neurons pālua i nā kāne i hana ʻia e Meth. ʻO ka mea i koe wale nō ka MEApd, kahi i loaʻa ai kahi hopena o ka moʻa ʻana ma nā helu o nā pūnaewele lepili ʻelua (F (9.991) = 0.006; p = XNUMX). Eia naʻe, ʻaʻohe hopena holoʻokoʻa o ka mālama lāʻau ʻana a me ka lepili ʻana i nā hui Meth i mālama ʻia ʻaʻole i ʻoi aku ke kiʻekiʻe ma mua o nā hui saline i mālama ʻia, no laila ʻaʻole i hoʻokumu ʻia e ka lāʻau2 Pūnaewele). ʻO ka lua, uaʻikeʻia nā wahi o ka lolo i kahi e hoʻokomoʻia ai ka ulupalaʻana e ka male (3 Pūnaewele). ʻO ke kaulike, ua hoʻohanaʻia ka MPN, BNSTpm, a me ka VTA wale nō ma ka mikiʻana, a ua loaʻa ka piʻi nui o Fos (F (1,16) = 14.99-248.99; pāʻani 0.001), akā,ʻaʻohe MER-hoʻokomoʻia pERK.

2 Pūnaewele      

'Iwehe o nāʻike FER a me ka Meth-i hoʻokomoʻia i loko o nā wahi lolo kahi e hoʻohana ai ka wahine i ka wahine a me nā lāʻau lapaʻauʻole i nā lāhui neural.
3 Pūnaewele      

'Iwehe o nāʻike FER a me nā Meth-i hoʻokomoʻia i loko o nā wahi lolo kahi i hoʻokomoʻia ai ka neural activation wale nō e ka male.

I ka hopena, ua loaʻa nā wahi o ka lolo ma kahi e ulu ai ka wahine a me nā lāʻau lapaʻau i nā heluna o nā neurons (Hōʻike 2 a A me3) .3). I ka NAc a me ka iwi, BLA, a me ACA, aia nā hopena āpau o ka male ʻana (F (1,16) = 7.87-48.43; p = 0.013- <0.001) a me ka lāʻau lapaʻau (F (1,16) = 6.39– 52.68; p = 0.022- <0.001), a me ka launa pū ʻana ma waena o kēia mau mea ʻelua (F (1,16) = 5.082-47.27; p = 0.04- <0.001; ʻaʻohe pilina koʻikoʻi ma ACA) ma nā helu o nā hunaola e hōʻike ana i nā mea ʻelua hoʻokomo ʻia ʻo Fos a me Meth i hoʻokomo ʻia e Meth. Ua hōʻike ʻia ka loiloi Post hoc ʻoi aku ka nui o nā neurons i hōʻailona ʻia ʻoi aku ka nui ma nā kāne i hana ʻia Meth-injected i hoʻohālikelike ʻia me Meth-treated (p = 0.027- <0.001), a i mālama ʻia nā saline saline (p = 0.001- <0.001) kāne (Hōʻike 2 a A me3) .3). I ka hōʻoiaʻana o nāʻikepili e like me nā pākēkē o nā neuronui i hoʻohanaʻia i ka lāʻau, 39.2 ± 5.3% i ka papa NAc, 39.2 ± 5.8% i ka shell NAc, 40.9 ± 6.3% i ka BLA, a me 50.0 ± 5.3% o nā neurons ACA. ʻo lāua a me Meth.

Hōʻike 2      

Nā hoʻopiʻi PERK i hoʻopiliʻia me ka Meth e hoʻokomoʻia ma nā neo XAXX,ʻo BLA, a me ACA ma hope o ka hoʻolālā o 10 mg / kg Meth. ʻO ka helu maʻamau o ka hapa o Fos (a, d, g, j), pERK (b, e, h, k), a me nā pūnaewele i kālua (c, f, i, l) i loko o ka papa NAc (a, ...

ʻO ka nānāʻana i ka nānāʻoleʻia,ʻo ka hoʻopiliʻana i ka pERK Meth-induced. ʻOiai ua hoʻoikaika nuiʻiaʻo Meth i nā kinona ma nā lālā Meth-injected māmā a me kaʻole i ka NAC, BLA, a me ACA, he kaha haʻahaʻa loa ka labeling pERK i nā kāne male Meth-injected i ka hoʻohālikelikeʻana i nā kāne Meth-injected (Hōʻike 2b, e, h, k; p = 0.017- <0.001). Hiki paha i kēiaʻike ke kākoʻo i ke kuhiakau i ka hanaʻana o ka wahine a me nā lāʻau lapaʻau i kēlā mau aihu like, akā, he mea hōʻailona paha ia i ka hoʻololiʻana i ka hoʻololi i loko o ka lāʻauʻona a iʻole ka hopena o ka mea i hoʻololi i nā pane i ka Meth. No kaʻimi i kaʻike inā heʻano likeʻole keʻano o ka hanaʻana i nā lāʻau i hoʻohuiʻia, ua hoʻopauʻia nā māhele o ka NAc, BLA, a me ACA no nā kāne i mōhaiʻia ma kahi manawa hope loa (15 min) ma hope o ka hoʻoponopono lāʻau (hoʻokolohua 2).

Hōʻikeʻo 2:ʻO kaʻike o nā pūnaewele i hoʻopaʻaʻia a me nā lua i hoʻopaʻa i nā hopena i hōʻikeʻia ma luna aʻe nei i ka moe kolohe a me ka hōʻikeʻana i nā Meth 15 mau minuke ma mua o ka mōhai i loaʻa ai ka piʻi nui o Fos a me pERK immunolabeling ma ka NAC kumu a me ka shell, BLA, a me ACA. Eia kekahi, uaʻike houʻia kekahiʻano hāʻina-nui o ka PERK i hoʻokomoʻia i loko o ka pilina a me ka Meth-induced pERK ma kēia mau wahi (Hōʻike 4; hopena male: F (1,12) = 15.93–76.62; p = 0.002- <0.001; hopena lāʻau: F (1,12) = 14.11-54.41; p = 0.003- <0.001). ʻOi aku ka nui o nā neurons i hōʻailona ʻia i nā kāne i hoʻopili ʻia ʻo Meth i ʻoi aku ka kiʻekiʻe ma mua o ka Meth-treated (p <0.001) a i ʻole nā ​​kāne i mālama ʻia (p <0.001) kāne Ke hōʻike ʻia ka ʻike e like me nā pākēneka o nā neurons i hoʻohana ʻia i ka lāʻau, 47.2 ± 5.4% (NAc core), 42.7 ± 7.6% (NAc shell), 36.7 ± 3.7% (BLA), a me 59.5 ± 5.1% (ACA) o nā neurons i hoʻoulu ʻia e ka male ʻana ua hoʻoulu ʻia hoʻi e Meth. Eia kekahi, ʻaʻole ʻokoʻa ka PERK i hoʻokomo ʻia i ka lāʻau ma waena o nā holoholona i hoʻomoʻa ʻia a me nā holoholona ʻole (Hōʻike 4b, e, h, k), i nā wahi āpau koe ka ACA (p <0.001). Kuhi kēia mau ʻike i ka lawena moekolohe i ke kumu o ka hoʻololi ʻana i ke kumu kūlohelohe o ka hoʻokomo ʻia ʻana PERK na Meth.

Hōʻike 4      

Nā hoʻopiʻi PERK i hoʻopiliʻia me ka Meth e hoʻokomoʻia ma nā neo XAXX,ʻo BLA, a me ACA ma hope o ka hoʻolālā o 15 mg / kg Meth. ʻO ka helu maʻamau o ka hapa o Fos (a, d, g, j), pERK (b, e, h, k), a me nā pūnaewele i kālua (c, f, i, l) i loko o ka papa NAc (a, ...

Nā Neural Activation ma muli o ka moe kolohe a me ka 1 mg / kg Meth

Ma ka hopena o nā hualoaʻa i hōʻikeʻia ai, ua hana ka halihaliʻana me ka 4 mg / kg Meth i nā heluna o nā neurons ma ka NAC a me ka shell, BLA, a me ACA. Tʻo ia e nānā i ka hopena o nā lāʻau lāʻau i kēia hanana i ka hoʻouluʻiaʻana, ua aʻoʻia hoʻi nāʻano o ka hoʻouluʻuʻana i ka neural ma ka hoʻohanaʻana i ka māhele haʻahaʻa o Meth. Ua nānāʻia ka NAc a me ka shell, BLA, a me ACA no ka hoʻouluʻana i hoʻokomoʻia e ka wahine a me Meth. ʻO kaʻoiaʻiʻo,ʻo ka moe kolohe a me ka hōʻikeʻana ma mua o Meth ka hopena nui o ka Fos a me ka pERK immunolabeling ma NAc core a me nā lalo lalo, ka BLA, a me nā neu ma ka ACA o ka mPFC (Hōʻike 5). ʻO ka mea e mahalo ai,ʻo ka māhele haʻahaʻa o Meth ka hopena o nā helu likeʻole o nā neerons i kahakahaʻia e 4 mg / kg Meth ma nā māheleʻehā e nānāʻia. ʻO ka mea nui aku,ʻo ka pilina NAc a me ka shell, BLA, a me ACA ka hōʻike i ka piʻi nui o ka helu o nā pūnaewele lua i kahakahaʻia (Hōʻike 5c, f, i, l) hoʻohālikelike ʻia me nā kāne kāne a inj-Meth injected (p = 0.003- <0.001). I ka hōʻike ʻia ʻana o ka ʻike e like me nā pākēneka o nā neurons i hoʻōla ʻia e ka lāʻau, 21.1 ± 0.9% a me 20.4 ± 1.8% ma ke kumu NAc a me ka pūpū, 41.9 ± 3.9% i ka BLA, a me 49.8 ± 0.8% o nā neurons ACA i hoʻoulu ʻia e ka moekolohe. a me Meth.

Hōʻike 5      

Nā hoʻopiʻi PERK i hoʻopiliʻia me ka Meth e hoʻokomoʻia ma nā neo XAXX,ʻo BLA, a me ACA ma hope o ka hoʻolālā o 15 mg / kg Meth. ʻO ka helu maʻamau o ka hapa o Fos (a, d, g, j), pERK (b, e, h, k), a me nā pūnaewele i kālua (c, f, i, l) i loko o ka papa NAc (a, ...

Ka Neural Activation ma muli o ka moekolohe a me ka hoʻoponoponoʻana o d-Amphetamine

No ka hōʻoia inā ua pololei nā hualoaʻa i luna no Meth, ua hoʻonuiʻia kahi hoʻokolohua'ē aʻe e aʻo i ka hoʻouluʻana i ke kekona. ʻO kaʻike o nā pūnaewele i hakuʻia a hoʻokahi mau lua no ka PERK a me ka Fos i hōʻikeʻia i ka hana maʻamau a me ka hōʻikeʻana i Amph ma muli o ka piʻi nui o Fos a me pERK immunolabeling ma ka NAc core a me ka shell a BLA (Hōʻike 6; hopena male: F (1,15) = 7.38-69.71; p = 0.016- <0.001; hopena lāʻau: F (1,15) = 4.70-46.01; p = 0.047- <0.001). Eia kekahi, ʻoi aku ka nui o nā neurons i hōʻailona ʻia me nā Amph i mālama ʻia e hoʻohālikelike ʻia me Amm i mālama ʻia (p = 0.009- <0.001), a i mālama ʻia paha nā saline saline (p = 0.015- <0.001) kāne (Hōʻike 6c, f, i). I kaʻikeʻana o kaʻikepili i nā hapa o nā neuronui i hoʻohanaʻia i ka lāʻau, 25.7 ± 2.8% a me 18.0 ± 3.2% i loko o ka NAc kumu a me ka pūʻano hoʻokahi, aʻo 31.4 ± 2.0% o nā neuron BLA i hoʻopiʻiʻia e nā mea male a me Amph. ʻO ka'āpana ACA o ka mPFC hōʻike i nā kūlana koʻikoʻi o nā Fos i hoʻokomoʻia i kaʻikepili (Hōʻike 6j; F (1,15) = 168.51; p <0.001). Eia naʻe, ʻokoʻa ka Meth, ʻaʻole hopena ʻo Amph i ka hoʻonui nui ʻana i nā pae pERK i hoʻokomo ʻia i ka lāʻau i loko o ka ACA (Hōʻike 6k) aiʻole nā ​​helu inoa o nā neurons i kahakahaʻia ma ka ACA (Hōʻike 6l) ke hoʻohālikelikeʻia i nā kāne male a me ka maleʻole.

Hōʻike 6      

Nā hoʻopiʻi pERK i hoʻokomoʻia i ka hoʻopiʻi me ka AmpH i nā neerons NAc, BLA, a me ACA 15 min ma hope o ka hoʻolālā o 5 mg / kg Amph. ʻO ka helu maʻamau o ka hapa o Fos (a, d, g, j), pERK (b, e, h, k), a me nā pūnaewele i kālua (c, f, i, l) i loko o ka papa NAc (a, ...

KA HOOHOLO

Ke hōʻike nei ka haʻawina o kēia manawa ma kahi laulā ma waena o ka hoʻouluʻana i nā neural i ka hoʻoikaikaʻana i ka moekolohe a me ka psychostimulant Meth. No laila, hōʻikeʻia kēia mauʻikeʻaʻole hoʻohana wale i nā lāʻau lapaʻau ma nāʻaoʻao'ekepili e hoʻoponopono ai i ka uku kūlohelohe, akāʻo ka meaʻoiaʻiʻo, hoʻohanaʻia nā lālā e like me ka hoʻoponopono o ka uku kūlohelohe. ʻO keʻano, ua hōʻikeʻia maʻaneʻi ua hoʻohuiʻia ka hana maʻamau a me Meth e ka lehulehu o nā neurons ma ka moku NAc a me ka shell, BLA, a me ACA o ka mPFC, eʻike ana i kahi mau pūnaewele e hiki ai iā Meth ke hoʻoweliweli i ka moekino.

ʻO kaʻike i kēia manawa e hoʻohālike ka halihali a me ka hoʻomaluʻana o nā mimiki kahuliʻana o nā neurons ma NAc, BLA, a me ACA i nāʻike mai nā haʻawina'ē aʻe e hōʻike ana i ka nui o ka heluna o nā neo Nele e hoʻopiʻi i ka uku lāʻau a me ka waiwai maoli.

ʻO keʻano,ʻo nā haʻawinaʻikepili e hoʻohālikelikeʻia i ka hoʻohuiʻiaʻana o ka neural i ka manawa o ka hoʻoponoponoʻana i nā hana kūlohelohe (ka meaʻai a me ka wai) a me ka cocaine i lokoʻole, ua hōʻikeʻia ka hoʻoponoponoʻiaʻana o ka cocaine e kekahi mau mea'ē aʻe, a me ka meaʻai (92%). ʻO 8% wale nō nā hōʻailona kūkā i hōʻikeʻia i ka hoʻoukaʻia e nā cocaine a me ka uku maoli (Kulanui a me., 2000).

Akā,ʻo ka hapa nui (65%) o ka pūnaewele i ka NAC ua hōʻikeʻia ka hoʻouluʻana e nāʻano kūlohelohe maoli (meaʻai a me ka wai),ʻoiai inā uaʻoi aku ka palakaʻana o kekahi mea hoʻoikaikaʻia (sucrose) (Roop et al., 2002).

ʻO kekahi mau kumu i hiki ke kōkua i ka kuhiʻana i nā hopena o kēia manawa. ʻO ka mea mua, ua hoʻohanaʻia nāʻano hanaʻokoʻaʻano'ē aʻe eʻimi i nā hana o ka neural. Ua hoʻohanaʻia ka hoʻohanaʻana i keʻano neuroanatomika no kaʻikeʻana o nā hanana neural likeʻole e nā hanana likeʻoleʻelua e hoʻohana ana i ka immunocytochemisty hou no Fos a me ka pERK, eʻae ai i ka hoʻolālāʻana o ka hoʻoikaikaʻana o ka pūnaewele ma luna o nā ākea nui o nā wahi lolo. I ka hoʻohālikeʻana, ua hoʻohanaʻia e nā kula a Carelli a me nā hoahanahana i nā mele mele i hoʻohuiʻia i ka NAc o ka hana holoholona e hoʻoponopono ai i ka hoʻoponopono ponoʻana o ka hoʻoponoponoʻana i nā lāʻau lapaʻau i ke kaʻina hana āpau.

ʻO ka lua, uaʻimi ke noi i kēia manawa i kahiʻokoʻa kūlohelohe'ē aʻe e pili ana i ka moekolohe i ka nānāʻana i nā haʻawina mua, ka mea i hoʻohana i ka meaʻai a me ka wai ma nāʻiole i kauʻia (Kulanui, 2000). ʻO kaʻai a me ka wai eʻoi aku ka maikaʻi ma mua o ka male. He mea nui ka hoʻomehana 'ana i ka wahine a hiki i nāʻiole ke hoʻokomo i CPP no ka hoʻopili (Agmo a me Berenfeld, 1990, Martinez a me Paredes, 2001, Tenk, 2008). ʻOiai, e hana nāʻiole i kāohi i CPP no ka wai (Agmo et al., 1993, ʻO Perks a me Clifton, 1997) a me ka meaʻai (ʻO Perks a me Clifton, 1997), dʻO nāʻiole i hoʻolālāʻoleʻia ka maikaʻi a me ka hoʻolālā CPP no nā meaʻai hiki keʻaiʻia (Jarosz et al., 2006, Jarosz et al., 2007).

ʻO ke kolu,ʻo kā mākou mau aʻoʻana he likeʻole nā ​​lāʻau lapaʻau i hoʻohanaʻia ma ka hoʻohālikeʻana i nā haʻawina mua, e hoʻohana ana i ka methamphetamine a me ka amphetamine ma mua aʻe o ka cocaine. Hōʻike nā hopena o kēia manawaʻo Meth a me ka amphetamine ka liʻiliʻi, ua hoʻoholoʻia ka hoʻonāʻana i nā neurons e hanaʻia e ka moe kolohe. Ma muli paha o kaʻikeʻana i ka hopena o ka lāʻauʻona, he mea nui ia i kā mākou mauʻike. Hoʻohanaʻia nāʻike i kēia manawa e nā holoholona iʻike kinoʻia, akāʻo ka lāʻau lapaʻau maoli. I ka hoʻokaʻawaleʻana, ua hoʻohana nā haʻawina koho electrophysiological no Carelli a me nā hoahanahana i nā holoholona "i hoʻonaʻauaoʻia" i loaʻa i nā manawa hou i ka cocaine.

No laila, hiki ke hanaʻia ka Meth e hoʻokomo i nā neurons e hanaʻia e ka moe kolohe i nāʻiole iʻikeʻia. Eia naʻe,ʻo nā haʻawina mua loa mai kā mākou papahana e hōʻike ana he mea nuiʻole kaʻikeʻana i ka lāʻauʻona i ka hana maʻamau a me ka maʻamau Meth i nā kāne i hanaʻia me Meth e like me nā mea likeʻole o nā neuronui i hoʻohanaʻia e like me ka mea i hōʻikeʻia ma ka papahana o kēia manawa. (20.3 ± 2.5% i ka NAc a me ka 27.8 ± 1.3% i ka mole NAc;

I ka hopena, uaʻimi ka noi i kēia manawa i ka hana "kuhikuhi" o nā lāʻau lapaʻau e hoʻohana ana i ka lawelawe hoʻomalu. No laila, 'aʻole hōʻike ka' ikepili o kēia manawa i nā 'ike e pili ana i nā'eneke āpau e pili ana i ka huli' ana i ka lāʻau a huli paha i pili i ka uku lāʻau, akā e hōʻike i nā hana kuʻuna i hanaʻia e ka hana pharmacological o ka lāʻau. Ma nā haʻawinaʻikepili'elepili mua,ʻo ka hanaʻana o ka nec Nec i loko o nā kekona o nā pane hoʻoikaikaʻia,ʻaʻole ia he hopena o ka hana o ka cocaine, akā ua hilinaʻi loa i nāʻano pilina ma loko o ka'ōnaehana hoʻomalu pono'ī (Kulanui, 2000, Kulanui, 2002). ʻO ke kolamuʻana, ua hoʻohuliʻia ka hana o ka NAc e nā pane hoʻokaʻawale a paneʻoleʻia o nā hanu e pili ana i ka hoʻopukaʻana i ka cocaine a me nā meaʻoki pūʻia (ʻo ia hoʻi, ke kikiʻana) i loko o kēia hiʻohiʻona hana (Kulanui, 2000, Kulanui a me Iames, 2001, Kulanui, 2002, Kulanui a me Wightman, 2004). Ma ka hōʻuluʻuluʻana, hiki ke hoʻomaopopo ponoʻia kā mākou mauʻike o ka hoʻoukaʻiaʻana e ka hana kūlohelohe a me ka lāʻau lapaʻau no ka hoʻouluʻia e ka moekino a me ka lawelawe Meth a me Amph.

Meth a me nā wāhine e piʻi ana i ka nui o nā neurons ma ka NAc kumu a me ka hāmeʻe i keʻano o keʻano. Hiki i nā mea hana pū i ka NAC ke hana i ka pale i nā hopena o Meth ma ka hoʻonāukiukiʻana a me ka uku waiwai o ka moekolohe me nā maʻi o ka NAC e hoʻopilikia i ka moe kolohe (Liu et al., 1998, Kippin et al., 2004). Eia kekahi,ʻo kēia mau neurons he wahi maʻamau no nā hopena o ka lāʻau no ka piliʻana i ka hopena ma muli o ka emiʻana o ka Meth (1 mg / kg) ma ka 50% i ka helu kiʻekiʻe o Meth (4 mg / kg). ʻOiaiʻaʻole kēia hōʻike e hōʻike ana i ka hōʻaho melepili o nā neurons hui pūʻia, ua hōʻikeʻia nā mea i hala mua e hōʻike ana i ka pERK a me ka Fos i hoʻokomoʻia i loko o ka NAC e hilinaʻi ana i ka dopamine (DA) a me nā mea loaʻa i ka glutamate (Valjent et al., 2000, Ferguson et al., 2003, Valjent et al., 2005, Sun et al., 2008). ʻOiaiʻaʻole i maopopo i ka hoʻoikaikaʻiaʻana o nā neural i hoʻokomoʻia ma ka NAC ma luna o kēia mau loea, ua hōʻikeʻia kēia ma nāʻaoʻao'ē aʻe, ma kahi o ka medial preoptic (Lumley lāuaʻo Hull, 1999, Dominguez et al., 2007). Thiki i ka male, ke hana i nā neurons i ka hana i ka wā o ka moe kolohe ma o ka hoʻomehanaʻana o ka dopamine a me nā mea loaʻa ka glutamate. ʻO ka hana o NAc glutamate ma ka moekino maʻamau i kēia manawa, akā, ua paʻa ka paʻaʻana o ke DA i ka hana koʻikoʻi ma ka hoʻoikaikaʻana no ka moe kolohe (Hull et al., 2002, Hull et al., 2004, Pfaus, 2009). ʻIkeʻia nā hua'ōlelo Microdialysis i ka piʻiʻana o ka NAc DA efflux i nā manawa kūpono a me ka hoʻopau o nā moe kāne kāne (Fiorino a me Phillips, 1999a, Lorrain et al., 1999) a me ka mesolimbic DA efflux ua hoʻopiliʻia i ka hoʻoikaikaʻana a me ka mālamaʻana i ka moe kolohe male (ʻO Pfaus a me Everitt, 1995). Eia kekahi, ua hōʻikeʻia nā hana hoʻoponoponoʻana a Mike i nā poʻe kū'ē'ē ma ka NAC e hōʻole i ka moekolohe, akāʻo ka mea hanaʻino e kōkua i ka hoʻomakaʻana i ka moe kolohe.r (Everitt et al., 1989, ʻO Pfaus a me Phillips, 1989). Penei, hiki i Meth ke hoʻopili i ka hoʻonāukiuki no ka moe kolohe ma o ka hoʻoukaʻana o nāʻelele.

I ka hoʻohālikeʻana i ka NAc, ua mau ka helu o nā pūnaewele i hoʻopaʻaʻia ma BLA a me ACA i ka mea i hoʻololiʻoleʻia e like me ka Meth. He mea koʻikoʻi ka BLA no ka hoʻonaʻauao kūikawā kūikawā a ke ikaika nui nei i ka hoʻouluʻana a me ka uku i ka loiloi ma kahi o nā mea kani (Everitt et al., 1999, Cardinal et al., 2002, E nānā, 2002). Hoʻopiʻiʻia nāʻioleʻeleʻele o BLA i ka hoʻoihoʻana i ka leve no nā kūpikipikikikikiko i hui pūʻia me kaʻai (Everitt et al., 1989) aiʻole ka hoʻoikaika kinoʻana (Everitt et al., 1989, Everitt, 1990). I ka hoʻokaʻawaleʻana,ʻaʻole e hoʻopili kēia hoʻoponopono i ka hopena kūpono o ka hānaiʻana a me ka moekino (Cardinal et al., 2002). He kī koʻikoʻi nō hoʻi ka BLA i ka hoʻomanaʻoʻana i nā kūpikipikipikena i pili i nā kumuhana lāʻau (Grace a Rosenkranz, 2002, ʻO Laviolette a me Grace, 2006). Nā leona a iʻole nā ​​hana hana kālaiʻike o ka BLA poraka i ka loaʻa (Whitelaw et al., 1996) a me ka'ōlelo (Grimm aʻike, 2000) ka hoʻouka houʻana i ka cocaine, akā naʻeʻaʻole e pili ana i ke kaʻina o ka hoʻoponopono lāʻau. Eia kekahi, Ua hoʻokomo kokeʻo Amph i nā hualoaʻa BLA i kahi hoʻouka houʻana i ka lāʻau i mua o nāʻike i kauʻia (E nānā a me al., 2003). No laila, hiki i ka psychostimulant-i hoʻonuiʻia ka hoʻopiʻiʻana o DA i nā hualoaʻa BLA i ka hoʻomanaʻoʻana o ka naʻau a me ka huliʻana. (Ledford et al., 2003) o ka moekolohe, no laila e hāpai ana i ka hoʻouluʻana i ka moe kolohe a me ka makemake i hōʻikeʻia e nā mea hoʻomāʻewaʻewa Meth (Semple et al., 2002, ʻO Green a me Halkitis, 2006).

I loko o ka ACA,ʻo ka hanaʻana o nā neuron i hoʻopaʻaʻia i ka wahine-he mea kūʻokoʻa a he kiko'ī no Meth, no ka mea,ʻaʻole iʻikeʻia me Amph. ʻOiaiʻo Meth a me Amph kekahi mauʻano hoʻolālā likeʻole a me nā mea kanu hoʻomanaʻo,ʻo Meth ka meaʻoi aku kaʻoi aku o ka ikaika ma mua o ka'AmH me nā hopena lōʻihi (NIDA, 2006). Nā Papaʻauao na Goodwin et al. ua hōʻikeʻo Meth i kahi keu DA efflux nui a hoʻopiʻi i ka hoʻokuʻuʻana o ka mea i hoʻohanaʻia ma kahi o ka'āina aʻoi aku ka maikaʻi ma ka'īlioʻo NAcʻoi aʻe o ka Amph. Hiki i kēia mau hiʻohiʻona ke hoʻohui i nā mea hoʻonani o Meth i ke kūlike me Amph (Goodwin et al., 2009) a ma muli paha o kaʻokoʻaʻana o keʻano o ka hanana i waena o nā lāʻau lapaʻauʻelua. Eia naʻe,ʻaʻole maopopo kaʻikeʻana o nāʻano likeʻole o nā hopena ma muli o nāʻano likeʻole ma waena o nā lāʻau lapaʻau a me nā pilikia e pili ana i nā lāʻau i hoʻohanaʻia a me ka hoʻokolokolo houʻana.

ʻAʻole iʻikeʻia ka hoʻouluʻana e Meth a me ka wahine ma nā papahana'ē aʻe o ka mPFC (IL a me PL). I loko o ka iole, ua loiloi nuiʻia ka ACA ma o ka hoʻohanaʻana i nā hana e'ākau ai, e kākoʻo ana i kahiʻoihana i nā kaiaulu hoʻokūkū (reinforus-reinforcer associations)Everitt et al., 1999, E nānā, 2002, Cardinal et al., 2003). Loaʻa nā hōʻike kūpono e pili ana ka mPFC i ka makemake i ka lāʻau a me ka hoʻihoʻiʻana i ka hana noiʻi a me ka lāʻauʻaina i loko o nā kānaka a me nāʻiole (Grant a me., 1996, Childress et al., 1999, Capriles et al., 2003, McLaughlin a me See, 2003, Shaham et al., 2003, ʻO Kalivas a me Volkow, 2005). ʻO waui ka laina a me kēia, ua hoʻohālikelikeʻia e hiki i ka hana o ka mPFC ma muli o ka hōʻike pinepineʻana i ka lāʻau hoʻomāinoino paha ke kuleana no ka hoʻouluʻana i ka hoʻoikaika a me ka hoʻomāhuahuaʻana i ka hana lāʻau i mālamaʻia e like me ka mea iʻikeʻia i loko o nā mea addicts (ʻO Jentsch a me Taylor, 1999). Hōʻike houʻia nāʻikepili hou mai kā mākou hale hōʻikeʻike i loaʻa nā hopena mPFC i ka hoʻomauʻana i kaʻimiʻana i ka moe kolohe i ka wā e pili ana kēia i kahi hoʻouluʻana (ʻO Davis et al., 2003). ʻOiaiʻaʻole kēia hana iʻimi i ka ACA, hiki ke kākoʻo i ke kuhiakau e pili ana ka MPFC (a me ka ACA) i nā hopena o Meth ma ka naloʻana o ka mana hana hoʻopunipuni e like me ka hōʻikeʻia e nā mea hoʻomāʻewaʻewa Meth (Salo et al., 2007).

Ma ka hopena, e pili ana kēia mau haʻawina i kahi kaʻina mua loa i ka hoʻomaopopo maikaʻiʻana i ka hoʻohanaʻana o nā lāʻauʻona i nā hana kuʻuna i ka hana maʻamau. Eia kekahi, ua hōʻike kēia mauʻike ma kaʻokoʻa i ka manaʻo o kēia mau lā,ʻaʻole hiki i nā lāʻau lapaʻau ke hoʻonā i nā pū like i loko o ka pūnaewele mesolimbic e like me ka uku maoli, Meth, a i ka mea liʻiliʻi nui loa, hoʻonāukiʻia nā pū like like me ka moekino. I ka huliʻana, hiki i kēia mau hana kuʻuna i hanaʻia i ka hoʻonaʻauaoʻana i ka huliʻana i ka waiwai kūlohelohe ma hope o ka hōʻailona lāʻau. I ka hopena, hiki i nā hopena o kēia aʻoʻana keʻano nui i ko mākou hoʻomaopopo i ke kumu o ka mea hōʻaia i keʻano maʻamau. Hoʻohālikelike i nā mea like a me nāʻano'ē aʻe, a me nā hoʻololiʻana i ka hoʻopiliʻana i nā neural o ka pūnaha mesolimbic i hoʻopiliʻia e ka moe kolohe e pili ana i ka lāʻau hoʻomāinoino e hiki ke alakaʻi i ka hoʻomaopopo maikaʻiʻana i ka hoʻohanaʻana i ka lāʻau a me nā hoʻololiʻana i ka uku kūlohelohe.

mau hoomaikai ana

Ua kākoʻoʻia kēia noiʻi ma nā haʻawina mai nā National Institute of Health a R01 DA014591 a me nā polokalamu o ka noiʻi olaola Canadian Canadian RN 014705 i ka LMC.

NĀ PONO

  • ABC
  • ʻo ka hanu avidin-biotin-horseradish peroxidase
  • ACA
  • kaʻaoʻao o mua
  • ʻO Amph
  • am amupetamine
  • BLA
  • amygdala nui
  • BNSTpl
  • ka hopena hōʻaho hope o ka stria terminalis
  • BNSTpm
  • ka pahu bedromedial bed of the stria terminalis
  • BT
  • ʻo ka biotinylated tyramide
  • CeA
  • cental amygdala
  • ʻO CPP
  • kahi makemake loa
  • E
  • ejaculation
  • EL
  • ka wāwae ejaculation
  • IF
  • wahi'āpana pahu
  • IL
  • ke kuhi hewa
  • IM
  • ke kū'ē
  • M
  • mauna
  • MAP Kinase
  • pūmua protein kinameʻa
  • MEApd
  • medieval medieval amygdala
  • Meth
  • methamphetamine
  • ML
  • mauna paʻa
  • mPFC
  • ka mediecal prefrontal cortex
  • MPN
  • ʻo ka preiatic medial preoptic nucleus
  • NAc
  • ʻAnakala Accumbens
  • PB
  • kūmau phosphate
  • PBS
  • Hoʻopihaʻia ka saline
  • ʻO PEI
  • ka lā ma hope o ka wā ejaculatory
  • PERK
  • MAP Kinase phosphorylated
  • PL
  • wahi'āpana
  • VTA
  • wahi'āpana o ka lehulehu

Nāʻaoʻao hemahema

Hoʻolaha Hoʻolaha o ka Publisher: He PDF PDF kēia o kahi palapala i hoʻohuiʻoleʻia iʻaeʻia no ka hoʻolahaʻana. Ma keʻano heʻoihana i kā mākou mea kūʻai, ke hoʻolako nei mākou i kēia papa mua o ka puke. E hana kopeʻia, kākauʻia, a me ka loiloiʻana o ka palapala kākau no ka hōʻoia hopena ma mua o ka paʻiʻiaʻana ma kāna pepa hope loa. Eʻoluʻolu, i ka wā o ka hanaʻana, eʻikeʻia nā hemahema e hiki ai ke hoʻopili i ka palapala, aʻo nā hewa āpau e pili ana i ka puke pai.

E hoʻomaopopo '

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