Methamphetamine na-eme ihe dị iche iche nke neurons na-achịkwa omume mmekọahụ na oke nwoke (2010)

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

Frohmader KS, Onye na-achọ ọrụ J, Onye maara ihe, Lehman MN, Coolen LM.

Source

Ngalaba mmepụta ihe na usoro ọgwụ ndụ, Ụlọ akwụkwọ ọgwụ na Schulich na Dentistry, Mahadum Western Ontario, London, ON, Canada, N6A 5C1.

nkịtị

Methamphetamine (Meth) bụ ihe na-akpali agụụ mmekọahụ. Mmegbu nke mmegbu na-ejikọtakarị na omume nke omume izere mmekọahụ na mmụba nke njikarị nke Human Immunodeficiency Virus na Meth na-akọ akụkọ na-abawanye agụụ mmekọahụ, mkpali, na mmekọahụ mmekọahụ. Ebumnuche nke ndu nke ọgwụ ọjọọ a abụghị ihe a maara. Nnyocha a na-amụ ugbu a na-egosi na nchịkwa Meth na oke ụmụ nwoke na-emepụta ụbụrụ na mpaghara ụbụrụ nke usoro mesolimbic bụ ndị na-emetụta ụkpụrụ omume mmekọahụ. Kpọmkwem, Meth na mating co-activate cell in the nucleus accumbens isi na shei, amygdala akpu, na cingulate cteulate cortex. Nchọpụta ndị a na-egosi na n'adịghị ka ọgwụ ọjọọ ndị a na-eme ugbu a na-eme ihe ike nwere ike ime otu mkpụrụ ndụ dị ka onye na-eme ihe ike, nke ahụ bụ omume mmekorita, ma n'aka nke ya, ọ nwere ike imetụta ịmanye ọchịchọ nke ụgwọ ọrụ a.

Keywords: ihe mgbagwoju anya na-ebuwanye ibu, amygdala dị ọcha, cortex mbụ, iji ọgwụ ọjọọ eme ihe, mmepụta nwa, ịṅụ ọgwụ ọjọọ

Ntugharị na ụgwọ ọrụ na-achịkwa site na usoro mesolimbic, netwọk njikọ nke akụkụ ụbụrụ gụnyere mpaghara mmebi (VTA) nucleus accumbens (NAc), amygdala dị ọcha, na cortox prefrontal (mPFC)Kelley, 2004, Kalivas na Volkow, 2005). E nwere ọtụtụ ihe àmà na-egosi na a na-arụ ọrụ mesolimbic na nzaghachi nye ma ihe abụọ nke mmegbu (Di Chiara na Imperato, 1988, Chang et al., 1997, Ranaldi et al., 1999) nakwa n'omume na-akwụghachi ụgwọ na-akwụghachi ụgwọ dị ka omume mmekọahụ (Fiorino et al., 1997, Balfour et al., 2004). Omume nwoke na nwanyị, na karịsịa ejaculation, na-akwụghachi ụgwọ dị ukwuu ma na-eme ka ụdị anụmanụ dị ike (Pfaus et al., 2001). Ụmụ òké na-etolite ebe a chọrọ (CPP) iji dochie ya (Agmo na Berenfeld, 1990, Martinez na Paredes, 2001, Tenk, 2008), ma ga - arụ ọrụ iji rụọ ọrụ iji nweta ohere nke nwanyi na -Everitt et al., 1987, Everitt na Stacey, 1987). Iji ọgwụ ọjọọ eme ihe na-akwụghachi ụgwọ ma na-eme ka ahụ sie ike, ụmụ anụmanụ ga-amụtakwa ịṅụ ọgwụ ọjọọ, gụnyere opiates, nicotine, mmanya, na psychostimulants (Onye maara ihe, 1996, Pierce na Daresan, 2006, Feltenstein na Lee, 2008). Ọ bụ ezie na a maara na iji ọgwụ ọjọọ eme ihe na omume mmekọahụ na-eme ka akụkụ ụbụrụ mesolimbic na-arụ ọrụ, ọ dị ugbu a ma ọ bụrụ na ịṅụ ọgwụ ọjọọ na-emetụta otu ihe ndị ahụ na-agbaso omume mmekọahụ.

Nnyocha nnyocha nke electrophysiological egosila na nri na cocaine na-arụ ọrụ dị na NAc. Otú ọ dị, ndị nkwado abụọ anaghị arụ ọrụ n'otu sel ahụ n'ime NAc (Carelli et al., 2000, Carelli na Wondolowski, 2003). Ọzọkwa, nri na sucrose nchịkọta onwe onye adịghị eme ka ọ bụrụ na ọ dị ogologo oge mgbanwe nke atụmatụ electrophysiological dị ka nke cocaine na-ebute (Chen et al., 2008). N'ụzọ dị iche, nchịkọta ihe àmà na - egosi na omume nwoke na nwanyị na iji ọgwụ ọjọọ eme ihe nwere ike ime ihe yiri otu mesolimbic. Psychostimulants na opioids na-agbanwe okwu nke omume mmekọahụ na oke oke (Mitchell na Stewart, 1990, Fiorino na Phillips, 1999a, Fiorino na Phillips, 1999b). Ihe omuma nke di na nyocha anyi gosiri na nmekorita nwoke na nwanyi na-eme ka ndi mmadu nwee ike imeghachi omume na ndi mmadu na-acho ihe ndi mmadu na-eme ka ha nwee ike ighota ha. (Pitchers et al., 2009). A na-ahụkarị nzaghachi yiri nke a mgbe ọ na-ekpughe ya na amphetamine ma ọ bụ ọgwụ ọjọọ ndị ọzọ (Lett, 1989, Shippenberg na Heidbreder, 1995, Shippenberg et al., 1996, Vanderschuren na Kalivas, 2000). Otu n'ime ihe ndị a na-enye echiche na ịkwa iko na azịza iji ọgwụ ọjọọ eme ihe na-eme ka ndị otu ntanetị ahụ dị n'usoro usoro mesolimbic gbazie ya. N'ihi ya, ebumnuche mbụ nke ọmụmụ ihe ugbu a bụ iji nyochaa mmechi nke usoro mesolimbic site na omume mmekọahụ na nchịkwa ọgwụ na otu anụmanụ. Karịsịa, anyị nwalere echiche ahụ bụ na psychostimulant, methamphetamine (Meth), na-eme ihe n'egbughị oge nke na-emekarị ka ọ bụrụ omume mmekọahụ.

Meth bụ otu n'ime ọgwụ ọjọọ ndị kachasị emegbu n'ụwa (NIDA, 2006, Ellkashef et al., 2008) naọ na-ejikọtakarị ya na omume mmekọahụ gbanwere. N'ụzọ na-akpali mmasị, ndị ọrụ Meth na-eme ka ọchịchọ mmekọahụ na mmetụ dịkwuo njọ, yana inwe mmasị mmekọahụ (Semple et al., 2002, Schilder et al., 2005). Ọzọkwa, A na-ejikọta mmegbu nke mmegbu na omume mkpasu iwe (Rawson et al., 2002). Ndị ọrụ na-ekwukarị na ha nwere ọtụtụ ndị mmekọ nwoke na nwanyị ma ọ dịkarịrị ka ha ga-eji nchedo karịa ndị ọzọ na-aṅụ ọgwụ ọjọọ (Somlai et al., 2003, Mmiri na al., 2007). N'ụzọ dị mwute, nchọpụta na-egosi Meth dị ka onye na-ekwu banyere omume izere mmekọahụ nwere oke dịka ha na-adabere na akụkọ ndị mmadụ na-ekwenyeghị na ya (Elifson et al., 2006). Ya mere, nnyocha a na-enyocha ihe gbasara mgbatị nke Meth na-eme mgbanwe n'omume nwoke na nwanyị na-achọ iji ghọta nke a na-agba ọgwụ ọjọọ.

N'ihi ihe akaebe a na-egosi na ọgwụ ọjọọ eme ihe, ma karịsịa Meth, nwere ike ime ihe ndị na-emetụtakarị ịkwa iko, ihe ebumnuche nke ọmụmụ ihe ugbu a bụ iji nyochaa mmebi imebi site na omume na nlekọta nke psychostimulant Meth. Ọmụmụ ihe a na-emejuputa usoro nyocha, nke na-eji ọgwụ ndị na-ahụ anya na-egosi ụdị mkpụrụ ndụ ihe nketa mbụ na Fos na phosphorylated Map Kinase (pERK) iji chọpụta ịlụ nwoke na nwanyị na Meth n'otu n'otu. A na-emepụta Fos naanị n'ime mkpụrụ ndụ nke mkpụrụ ndụ, ya na mpaghara nke 30-90 nke kachasị elu mgbe ọ gbanyechara ya. Enwere otutu ihe akaebe na mmekorita nwoke na nwanyi na-eme ka okwu Fos na ụbụrụ (Pfaus na Heeb, 1997, Ịhụ na Coolen, 1998), gụnyere usoro usoro mesocorticolimbic (Robertson et al., 1991, Balfour et al., 2004). Enwerekwa ihe akaebe na iji ọgwụ ọjọọ eme ihe na-emepụta okwu n'ime usoro mesocorticolimbic (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005). N'adịghị ka okwu nke Fos, phosphorylation nke ERK bụ usoro dị egwu ma na - eme 5-20 nkeji mgbe emechara ntọala. Ihe profaịlụ dị iche iche nke Fos na PERK na-eme ha ka ha bụrụ ihe dị mma nke akara maka ụbụrụ na-agbanyeghị na ntọala neuronal abụọ.

MGBE A GA-ECHICHE

Ndị isi

Dika okenye Sprague Dawley (210-225 g) nwetara site na Charles River Laboratories (Montreal, QC, Canada) nwere ụlọ abụọ n'ime ụlọ plexiglas. Ụlọ anụ ahụ nọgidere na-enwe na 12 / 12 h megharịrị ìhè ọkụ (ọkụ na 10.00 h). E nwere nri na mmiri ad libitum. A na-anwale ule niile n'oge ọkara nke ọkara n'ọchịchịrị na-acha ọkụ ọkụ. Umu nwanyi eji eme ihe n'omume di iche iche bu bilateral ovariectomized n'okpuru nrịkota di omimi (13 mg / kg ketamine na 87 mg / kg xylazine) ma nata ntinye nke subcutaneous nke nwere 5% estradiol benzoate (EB) na 95% cholesterol. Ndabere subcutaneous (sc) nke 500 μg progesterone na 0.1 ml sine oil 4 h tupu eswale. Usoro Nlekọta Ndị Na-ahụ Maka Ahụhụ nabatara usoro niile na Mahadum Western Ontario ma kwekọọ na ntụziaka nke Kansụl Canada na-elekọta nlekọta anụmanụ.

Ebube Nlereanya

Nlekọta 1 na 2: E nyere ụmụ irighiri nwa (n = 37) ka ha na nne na-anabata ihe na ejaculation (E) ma ọ bụ maka 30 min, nke batara mbụ na nyocha nyocha (60 × 45 × 50 cm) ugboro ise -emere ule tupu oge ule, iji nweta ahụmahụ mmekọahụ. N'ime oge abụọ ikpeazụ, e dekọrọ ihe niile edere maka arụmọrụ nke nwoke na nwanyị, gụnyere: nkwụsịtụ ugwu (ML, oge site na mmalite nke nwanyị ruo mgbe ugwu mbụ), mgbagha nke mgbochi (IL; oge site na ịbata nwanyị ruo n'ugwu mbụ abanye na ntancration), nkwụsị nke ejaculation (EL, oge site na mbụ mgbochi na ejaculation), biputere oge ejaculation (PEI, oge site na ejaculation na mberede ụmasị nke mbụ), ọnụ ọgụgụ nke mbadamba (M), na ọnụọgụ nke mpụ (IM)Agmo, 1997). Ụmụ nwoke niile natara 1 ml / kg kwa ụbọchị nke ọgwụ 0.9% NaCl (saline; sc) 3 ụbọchị ndị ọzọ tupu ụbọchị nyocha ahụ, n'ihi na ebe obibi maka njikwa na injections. Otu ụbọchị tupu ụbọchị ule ahụ, ụmụ nwoke niile na-alụbeghị di. N'ime ụmụ nwoke nwere ahụmahụ, Fos nwere ike ịmalite site na njirimara nke ọnọdụ ndị metụtara mmekọrịta ahụmahụ tupu oge ahụ (Balfour et al, 2004). Ya mere, a na-eduzi ihe niile a na-eme na nchịkwa mgbe a na-elele ule ikpeazụ ahụ n'ụlọ ezinigwe (zere nke a na-ahụ anya) ka ọ ghara igbochi njikarị ọrụ ejiri mee ihe na ụmụ nwoke na-ejighị n'aka. A kesara ndị ikom n'ime ìgwè nyocha ise dị iche iche bụ ndị na-adịghị iche na ụdị ọ bụla nke mmekorita nwoke na nwanyị n'oge ikpeazụ nke oge abụọ (data egosighi). N'oge ule ikpeazụ ahụ, a ga-ahapụ ụmụ nwoke ka ha nọrọ na ụlọ ha ruo mgbe ha gosipụtara ejaculation (nwoke ma ọ bụ nwanyị) ma ọ bụ na ha anataghị nwanyị ibe (enweghị mmekọahụ). Akpanyere ụmụ nwoke niile bụ 60 minit ole na ole na-esote mmalite nke mating iji nye ohere maka nyocha nke Fos-expression. Ndị nwoke natara ọgwụ 4 mg / kg Meth ma ọ bụ 1 ml / kg saline (sc) (n = 4 ọ bụla), ma ọ bụ 10 (nyocha 1) ma ọ bụ 15 (nyocha 2) min tupu ịmịnye ọgwụ, maka nyochaa phosphorylation ọgwụ nke MAP kinase. Ọgwụgwọ na oge tupu infusion na-adabere na akụkọ ndị gara aga (Choe et al., 2002, Choe na Wang, 2002, Chen na Chen, 2004, Mizoguchi et al., 2004, Ishikawa et al., 2006). Ngalaba na - achịkwa gụnyere ụmụ nwoke na - adabeghị, ma natara Meth 10 (n = 7) ma ọ bụ 15 (n = 5) min tupu àjà, ma ọ bụ salin injection 10 (n = 5) ma ọ bụ 15 (n = 4) min tupu ịchụ àjà . Mgbe a na-achụ àjà, a na-edozi echiche maka immunohistochemistry.

3 Nlereanya: Ebe ọ bụ na e jiri Meth mee ihe na nchọpụta 1 na 2, e mere nchọpụta neuroanatomo ọzọ iji nyochaa ma ọ bụrụ na omume mmekọahụ na dose dị ala nke Meth na-eme ka usoro ọgwụ ndị na-adabere na mgbakwunye mmechi ahụ. A na-eme nchọpụta a n'otu ụzọ yiri 1 na 2. Otú ọ dị, na ule ikpeazụ, ndị na-eto eto na ndị na-adịghị ahụkebe (n = 6 nke ọ bụla) natara 1 mg / kg Meth (sc) 15 min tupu ịchụ àjà.

Nleta 4: Iji nwalee ma ọ bụrụ na ịmalite ịmalite mmekọahụ na Meth bụ kpọmkwem maka Meth, nchọpụta a na-enyocha ma a ga-ahụ ụdị ihe ndị ọzọ nke ịmalite ịmalite ịmalite ịmalite ime ihe na psychostimulant d-amphetamine (Amph). A na-eme nchọpụta a n'otu ụzọ ahụ dịka nyocha 1 na 2. Otú ọ dị, na ule ikpeazụ, a na-elekọta ụmụ nwoke ma ọ bụ Amph (5 mg / kg) ma ọ bụ saline (1 mg / kg) (sc) 15 min tupu àjà (n = 5 ọ bụla). Ido ụmụ nwoke na-enweghị ike natara Saline ma ọ bụ Amph 15 nkeji tupu àjà. A na-enyocha usoro nyocha nke ejiji 1-4 Isiokwu 1.

Isiokwu 1      

N'ihe banyere otu nnwale dị iche iche gụnyere 1-4.

Nkwadebe anụ ahụ

Anesthetized anụmanụ na pentobarbital (270 mg / kg; ip) ma jiri 5 ml saline soro 500 ml 4% paraformaldehyde na 0.1 M phosphate buffer (PB). E wepụrụ ụbụrụ ma tinyezie ya maka 1 h na ọnụ ụlọ okpomọkụ n'otu nhazi ahụ, tinyezie ya na 20% sucrose na 0.01% Sodium Azide na 0.1 M PB ma debe ya na 4 ° C. A na-ebipụta ngalaba coronal (35 μm) na microtome na-egbuke egbuke (H400R, Micron, Germany), na-agbakọta na usoro anọ dị na nchịkwa Cryoprotectant (30% sucrose na 30% ethylene glycol na 0.1 M PB) ma debe na 20 ° C ruo mgbe ọzọ nhazi.

Immunohistochemistry

A na-eme ihe niile a na-eme n'ime igwe dị ọkụ ma jiri obi nkoropụ mee ihe. Achachachaala ebe ndị na-ese n'elu mmiri na ntanetụ salin (0.1 M Phosphate) nke na-eme ka phosphate na-efe efe (PBS) dị n'etiti incubations. A kpalitere ngalaba na 1% H2O2 maka 10 min, wee gbochie ya na nghazi ngwakọta (PBS nwere 0.1% bovine serum albumin na 0.4% Triton X-100) maka 1 h.

PERK / Fos

A na-eme ka anụ ahụ na-egbuke egbuke na p42 na p44 map kinase ERK1 na ERK2 (PERK; 1: 400 nlele 1 nza 19; 1: 4.000 nyocha 2 na 3 nza 21: Cell Signaling Cat # 9101;), Ngwongwo 1 na biotinylated donkey anti-rabbit IgG (1: 500; Jackson Immunoresearch Laboratories, West Grove, PA) na avidin-horseradish peroxidase complex (ABC Elite; 1: 1000; Vector Laboratories, Burlingame, CA). Mgbe ahụ, a gbanyere anụ ahụ maka 10 min na biotinylated tyramide (BT; 1: 250 na PBS + 0.003% H2O2; Kọmitii Ngwá Ọrụ Nyocha nke Tyramid, NEN Life Sciences, Boston, MA) na maka 30 min na Alexa 488 conjugated strepavidin (1: 100; Jackson Immunoresearch Laboratories, West Grove, PA). Na-esote, anụ ahụ na-ejikọta ya na ngwongwo nke polyplonal rabbit megide c-Fos (1: 500; SC-52; Santa Cruz Biotechnology, Santa Cruz, CA), tinyere 30 min incubation na ewu rabbit Alexa 555 (1: 200; Laboratories Jackson Immunoresearch, West Grove, PA). Mgbe e mesịrị ya, a sachasịrị ngalaba ahụ na 0.1 M PB, na-etinye ya na ihe ngosi slides na 0.3% gelatin na ddH20 ma na-ekpuchi onye na-arịwanye elu na-arị elu (Gelvatol) nke na-ebu nje 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). Njigide ihe na-eme ka ọ bụrụ na ọ bụ ma ọ bụ maọbụ ma nje abụọ ahụ, na-akpata enweghị ntinye aha na ntụgharị ntụgharị kwesịrị ekwesị.

Nyocha data

Mmekọahụ

Maka nchọpụta anọ ahụ, edere ederede maka arụmọrụ na-edekọ dịka akọwara n'elu ma nyochaa site na iji analysis nke ọdịiche (ANOVA). Nyocha data banyere omume mmekọahụ n'oge ule ikpeazụ nke nyocha gosipụtara ọdịiche dị iche n'etiti ndị dị iche iche na mpaghara ọ bụla nke arụmọrụ mmekọahụ.

Nyocha / Ụgha Fos

A na - agụta mkpụrụ sel abụọ na abụọ maka Fos na PERK na ọkwa nke isi NAc na mpaghara ala mmiri, amygdala na-adịghị ọcha (BLA), nnọchite amygdala (MEApd), central amygdala (CeA), preoptic nucleus (MPN), postromedial na ihe mgbakwasị ụda nke stria terminalis (BNSTpm na BNSTpl), na ebe a na-atụgharị aka (ACA), prelimbic (PL), na mpaghara infralimbic (IL) nke mPFC. E weghaara foto site na iji kamera CCD nwere ume (Microfire, Optronics) nke ejikọtara na microscope Leica (DM500B, Leica Microsystems, Wetzlar, Germany) na ngwanrọ Neurolucida (MicroBrightfield Inc) na ntọala igwefoto edozi maka isiokwu niile (iji ihe mgbaru ọsọ 10x). Iji ngwanrọ neurolucida, akọwapụtara nchịkọta nke dabere na akara ngosi (Swanson, 1998) pụrụ iche maka mpaghara ụbụrụ ọ bụla (lee Nyocha 1). A na-eji usoro nyocha nke mpaghara mee ihe na mpaghara niile ma e wezụga NAc isi na shei. N'ebe ikpeazu, ikwu okwu na okwu Fos abụghị ihe jikọrọ ya ma gosipụta ya na ngwugwu. Ya mere, e depụtara isi na shei dịka akara ala (ventricle azụ, ntụrụndụ nke mbụ, na àgwàetiti Calleja). Mpaghara nyochaa adịghị iche n'etiti otu ụdị, ma 1.3 mm2 na NAc isi na shei. Mpaghara nke nyocha maka ebe ndi ozo bu: 1.6 mm2 na BLA, 2.5 na 2.25 mm2 na MEApd na CeA, 1.0 mm2 na MPN, 1.25 mm2 na BNST na mpaghara mPFC, na 3.15 mm2 na VTA. A gụrụ akụkụ abụọ bilaterally maka ụbụrụ ọ bụla na mpaghara ọ bụla anụmanụ, na ọnụ ọgụgụ nke sel abụọ na dual labeled maka PERK na Fos yana ntinye nke mkpụrụ ndụ PERK nke gosipụtara Fos marker. Maka nyocha 1, 2, na 4, a na-eji ọnụ ọgụgụ ndị otu tụnyere ụzọ abụọ ANOVA (ihe: mating na ọgwụ) na Fisher's LSD maka post hoc na-atụnyere na 0.05 dị mkpa. Maka ule 3, a na-eji ọnụ ọgụgụ ndị otu tụnyere iji t-ule na-enweghị atụ na 0.05 dị mkpa.

Nyocha 1      

Ihe osise na ihe osise na-egosi ebe ụbụrụ nyocha. Mpaghara nyocha e gosiri na-adabere na akara ama ama maka mpaghara mpaghara ụbụrụ ọ bụla, ọ dị iche n'etiti otu nnwale, ma bụrụ 1.25 mm2 na subregions mPFC (a), 1.3 mm2 na ...

Images

Foto di iche iche maka Nyocha 3 ejidera igwefoto CCD (DFC 340FX, Leica) ka ejikọtara na microscope Leica (DM500B) wee bubata n'ime Adobe Photoshop 9.0 software (Adobe Systems, San Jose, CA). Agbanweghị foto ọ bụla ma e wezụga n'ihi mgbanwe nke ncha.

Nyocha 3      

Ihe oyiyi ndị nnọchianya nke ngalaba NAC anaghị edozi maka Fos (ọbara ọbara; a, d, g, j) na pERK (akwụkwọ ndụ akwụkwọ ndụ; b, e, h, k) nke ụmụ anụmanụ nke ọ bụla nlereanya: Ọ dịghị Mmekọahụ + Sal (a, b, c) , Sex + Sal (d, e, f), Ọ dịghị Mmekọahụ + Meth (g, h, i), na Mmekọahụ + Meth (j, k, l). Ogwe aka ziri ezi bụ ...

IHE

Mmeghari nke usoro nke usoro uba site na mmekorita nke nwoke na nwanyi na nlekota nke Meth

Nlekọta 1: Nkọwapụta nke sel abụọ na ejiri abụọ maka ndị na-ejikọta na Fos na Meth nabatara ụmụ nwoke ndị natara Meth 10 nkeji tupu ịchọta onyinye Fing na-emetụta na MPN, BNSTpm, NAc na shell, BLA, VTA, na mpaghara mpaghara niile nke mPFC, na-emekọ na ọmụmụ ihe ndị na-egosi ntinye na-eme ka e nwee Fos okwu na mpaghara ndị a (Baum na Everitt, 1992, Pfaus na Heeb, 1997, Ịhụ na Coolen, 1998, Hull et al., 1999). Nchịkwa Meth 10 nkeji tupu ịchụ àjà a na-ebute na NAc isi na shei, BLA, MeApd, CeA, BNSTpl, na mpaghara nke mPFC, kwekọrọ na usoro mmezi nke ndị ọzọ psychostimulants batara (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005).

Ọzọkwa, a chọpụtara usoro atọ nke nkwupụta ụbụrụ nke mmekorita site na omume mmekọahụ na Meth: Nke mbụ, a chọpụtara ebe ụbụrụ bụ ebe mmekọahụ na ọgwụ ọjọọ na -Isiokwu 2). Kpọmkwem, na CeA, MEApd, BNSTpl, na mPFC, mmụba dị ukwuu ma na-ebute ọgwụ ọjọọ (F (1,16) = 7.39-48.8; p = 0.015- <0.001) na mmekọahụ na-emetụta Fos (F (1,16, 16.53) = 158.83-0.001; p <1,16) hụrụ. Agbanyeghị, na mpaghara ndị a enweghị mmụba dị ịrịba ama na akwara akwara akpọrọ n'ime ụmụ nwoke nwoke mesoro Meth. Nanị ihe dị iche bụ MEApd, bụ ebe achọtara nsonaazụ nke ọnụọgụ na ọnụọgụ nke mkpụrụ ndụ abụọ akpọrọ (F (9.991) = 0.006; p = XNUMX). Otú ọ dị, ọ dịghị mmetụta ọ bụla nke ọgwụgwọ ọgwụ na ịdebanye aha abụọ na ìgwè ndị a na-agwọ Meth adịghị elu karịa ndị otu a na-agwọ saline, n'ihi ya, ọ bụghị ọgwụ ahụ kpatara (Isiokwu 2). Nke abụọ, a chọpụtara ebe ụbụrụ bụ ebe mmịnye na-ejikọta ọkpụkpụ anụ ahụ (Isiokwu 3). Kpọmkwem, MPN, BNSTpm, na VTA na-arụ ọrụ nanị site na mating, ma nwere nnukwu mmụba na Fos (F (1,16) = 14.99-248.99; p ≤ 0.001), ma ọ dịghị Meth-emetụta ya.

Isiokwu 2      

N'ihe banyere okwu mmeghe nke Fos na Meth na-emetụta ụbụrụ n'eme ụbụrụ ebe mmekọahụ na ọgwụ ọjọọ na-eme ka ndị mmadụ ghara ịmịpụta ihe.
Isiokwu 3      

N'ihe banyere nkwupụta okwu Fos na Meth na-emetụta ụbụrụ na akụkụ ụbụrụ ebe mmezigharị mmezigharị na-emetụta nanị site na mating.

N'ikpeazụ, a chọpụtara ebe ụbụrụ ebe mmekọahụ na ọgwụ ọjọọ na -Nyocha 2 na Na3) .3). Na NAc isi na shei, BLA, na ACA, enwere mmetụta zuru oke nke ịlụ (F (1,16) = 7.87-48.43; p = 0.013- <0.001) na ọgwụgwọ ọgwụ (F (1,16) = 6.39–52.68) 0.022; p = 0.001- <1,16), yana mmekọrịta dị n'etiti ihe abụọ a (F (5.082) = 47.27-0.04; p = 0.001- <0.027; enweghị mmekọrịta dị mkpa na ACA) na ọnụọgụ mkpụrụ ndụ na-egosipụta ma mating-induced Fos na Meth na-emetụta PERK. Ihe nyocha nke post gosiri na ọnụ ọgụgụ nke akwara ozi abụọ a kpọrọ aha dị elu nke ukwuu na ụmụ nwoke ndị nwoke na-atụnyere Meth ma e jiri ya tụnyere Meth na-emeso ya (p = 0.001- <0.001), ma ọ bụ mesine saline mesoo (p = 0.001- <XNUMX)Nyocha 2 na Na3) .3). Mgbe e gosipụtara data dị ka pasent nke eriri ọgwụ, 39.2 ± 5.3% na isi NAc, 39.2 ± 5.8% na kọlụm NAc, 40.9 ± 6.3% na BLA, na 50.0 ± 5.3% nke ACA neurons ma mating na Meth.

Nyocha 2      

Mmekọahụ na Meth na-eme ka mmadụ nwee mmekọahụ na-ekwu okwu na ngwongwo NAc, BLA, na ACA 10 min mgbe nchịkọta nke 4 mg / kg Meth. Ọnụ ọgụgụ dịmimi nke Fos (a, d, g, j), pERK (b, e, h, k), na sel abụọ (c, f, i, l) na isi NAc (a, ...

Ihe a na-atụghị anya ya bụ na omume mmekọahụ metụtara Meth-induced pERK. Ọ bụ ezie na Meth bu ụzọ wepụta ọkwa dị iche iche na akụkụ Meth-injected, na NAc, BLA, na ACA, pingk labeling dị nnọọ ntakịrị karịa ụmụ nwoke na-arịa ọrịa Meth-injected ma e jiri ya tụnyere ụmụ nwoke Meth-injected (Dee 2b, e, h, k; p = 0.017- <0.001). Nchọpụta a nwere ike ịkwado nkwenye ahụ na mmekọahụ na ọgwụ ọjọọ na-eme otu ihe ahụ, ma ọ pụkwara ịbụ ihe na-egosi mgbanwe mgbanwe nke mgbochi na mgbochi ọgwụ ma ọ bụ metabolism na nke a na-eme ka Meth gbanwee usoro ntụgharị. Iji nyochaa ma ọ bụrụ na mmekorita nwoke na nwanyị na-eme ka ihe dịgasị iche iche nke ịmalite ịṅụ ọgwụ ọjọọ, akụkụ nke NAc, BLA, na ACA nwere ntụpọ maka ụmụ nwoke na-achụ àjà n'oge na-esote oge (15 min) na-eso nchịkọta ọgwụ (nyocha 2).

Nlekọta 2: Nyochaa nke sel abụọ na ejiri abụọ kwadoro nchọpụta ndị a kọwara n'elu na omume mmekọahụ na ikpughe ya na Meth 15 nkeji tupu ịchụ àjà mere ka enwekwu ọganihu nke Fos na ọgwụ immunolabeling na NAc na shell, BLA, na ACA. Tụkwasị na nke ahụ, a chọtara mkparịta ụka co-okwu nke Fos na Meth-induced pERK na mpaghara ndị a (Nyocha 4; mmekorita nke di na nwunye: F (1,12) = 15.93-76.62; p = 0.002- <0.001; mmetụta ọgwụ: F (1,12) = 14.11-54.41; p = 0.003- <0.001). Ọnụ ọgụgụ nke akwara abụọ a na-akpọ na ụmụ nwoke na-etinyere Meth dị nnọọ elu ma e jiri ya tụnyere ụmụ nwoke na-agwọ ọrịa Meth (p <0.001) ma ọ bụ ụmụ nwoke na-agwọ saline (p <0.001) Mgbe egosiri data dị ka pasent nke ụbụrụ na-arụ ọrụ ọgwụ, 47.2 ± 5.4% (NAc core), 42.7 ± 7.6% (NAc shell), 36.7 ± 3.7% (BLA), na 59.5 ± 5.1% (ACA) nke neurons arụ ọrụ. site na mating na-arụkwa ọrụ site n'aka Meth. Ọzọkwa, akwụkwọ a na-etinye ọgwụ adịghị iche n'etiti anụ ọhịa mated na anụmanụ na-adịghị mma (Dee 4b, e, h, k), na mpaghara niile ma e wezụga ACA (p <0.001). Ihe data ndị a na-egosi na omume mmekọahụ na-eme ka mgbanwe nke usoro ihe omume nke Meth na-ebute.

Nyocha 4      

Mmekọahụ na Meth na-eme ka mmadụ nwee mmekọahụ na-ekwu okwu na ngwongwo NAc, BLA, na ACA 15 min mgbe nchịkọta nke 4 mg / kg Meth. Ọnụ ọgụgụ dịmimi nke Fos (a, d, g, j), pERK (b, e, h, k), na sel abụọ (c, f, i, l) na isi NAc (a, ...

Mmechi na-arụ ọrụ na-akpata Mmekọahụ na 1 mg / kg Meth

Nsonaazụ dị ugbu a gosiri na àgwà mmekọahụ na 4 mg / kg Meth na-eme ka ndị mmadụ na-ekpuchi ọnụ ọgụgụ nke neurons na isi NAc na shea, BLA, na ACA. Tị na-enyocha mmetụta nke ọgwụ-dosage na nke a na-agabiga na mmalite, a na-amụkwa usoro nke mmezigharị na-eme ihe site na iji Meth dị ala. A na-enyocha isi NAc na shea, BLA, na ACA maka ịmalite ọrụ site na mmekọahụ na Meth. N'ezie, mmekorita nwoke na nwayo na Meth mere ka o nwekwuo mmelite nke Fos ma na-ekpochapu nje na mpaghara NAc na shea mmiri, BLA, nakwa neurons na mpaghara ACA nke mPFC (Nyocha 5). N'ụzọ na-adọrọ mmasị, ụda dị ala nke Meth mere ka ọnụ ọgụgụ ndị dị otú ahụ na-emepụta ihe dị ka 4 mg / kg Meth n'ime ụbụrụ ụbụrụ anọ a nyochara. Karịsịa, isi NAc na shea, BLA, na ACA gosipụtara mmụba dị elu na ọnụọgụ abụọ sel abụọ (Dee 5c, f, i, l) ma e jiri ya tụnyere ụmụ nwoke na-agbanyeghị na Meth (p = 0.003- <0.001). Mgbe egosiri data dị ka pasent nke ụbụrụ na-arụ ọrụ ọgwụ, 21.1 ± 0.9% na 20.4 ± 1.8% na isi NAc na shei n'otu n'otu, 41.9 ± 3.9% na BLA, na 49.8 ± 0.8% nke ACA neurons na-arụ ọrụ site na mmekọahụ. na Meth.

Nyocha 5      

Mmekọahụ na Meth na-eme ka mmadụ nwee mmekọahụ na-ekwu okwu na ngwongwo NAc, BLA, na ACA 15 min mgbe nchịkọta nke 1 mg / kg Meth. Ọnụ ọgụgụ dịmimi nke Fos (a, d, g, j), pERK (b, e, h, k), na sel abụọ (c, f, i, l) na isi NAc (a, ...

Mmechi na-eme ka ndị mmadụ nwee mmekọahụ na nlekọta nke d-Amphetamine

Iji nwalee ma ihe ndị ahụ e kwuru n'elu bụ kpọmkwem maka Meth, e mere nchọpụta ọzọ iji mụọ ihe gbasara ntụrụndụ- na ntinye aka na ntinye aka nke Amph-induced. Nyocha nke sel sel na abụọ maka akara na Fos gosipụtara na omume mmekọahụ na nkwupụta ụda na Amph mere ka enwewanye mmụba nke Fos na ịmepụta immunolabeling na NAc na shea na BLA (Nyocha 6; mmekorita nke di na nwunye: F (1,15) = 7.38-69.71; p = 0.016- <0.001; mmetụta ọgwụ: F (1,15) = 4.70-46.01; p = 0.047- <0.001). Ọzọkwa, ọnụ ọgụgụ nke akwara ozi abụọ a kpọrọ aha dị elu karịa nke Amph na-emeso ya ma e jiri ya tụnyere Amph-emeso ya (p = 0.009- <0.001), ma ọ bụ mesine saline mesoro (p = 0.015- <0.001) ụmụ nwoke (Dee 6c, f, i). Mgbe e gosipụtara data dị ka pasent nke eriri mmiri ọgwụ, 25.7 ± 2.8% na 18.0 ± 3.2% na isi NAc na shea dịka, 31.4 ± 2.0% nke eriri BLA na-arụ ọrụ site ma mating na Amph. Mpaghara ACA nke mPFC gosipụtara ọkwa dị ukwuu nke mating-induced Fos (Dee 6j; F (1,15) = 168.51; p <0.001). Agbanyeghị, n'adịghị ka Meth, Amph emeghị ka mmụba dị ukwuu na-ebute ọgwụ ọjọọ na ACA (Nyocha 6k) ma ọ bụ nọmba ọnụọgụ abụọ ejiri aka na ACA (Nyocha 6l) ma ọ bụrụ na e jiri ya tụnyere ụmụ nwoke na-esite na saline na-adịghị edozi ahụ.

Nyocha 6      

Mmekọahụ na Amph-induced Sex-induced ikwu okwu na NAc, BLA, na ACA neurons 15 min mgbe nchịkọta nke 5 mg / kg Amph. Ọnụ ọgụgụ dịmimi nke Fos (a, d, g, j), pERK (b, e, h, k), na sel abụọ (c, f, i, l) na isi NAc (a, ...

NKWASỊTA

Ihe omumu nke a na - egosi na onodu ogugu di iche iche na - adi elu n'agbata mmekorita nke mmekorita nke nwanyi na psychostimulant Meth. Ya mere, data ndị a na-egosi na ọ bụghị nanị na ịṅụ ọgwụ ọjọọ na-eme n'otu mpaghara ụbụrụ nke na-achịkwa ụgwọ ọrụ nkịtị, ma n'eziokwu, ọgwụ na-eme ka otu mkpụrụ ndụ ndị dị na ụkpụrụ nke ụgwọ ọrụ nkịtị. N'ụzọ doro anya, e gosipụtara ebe a na omume mmekọahụ na Meth na-eme ka ọnụ ọgụgụ ndị nọ na mpaghara NAc na shei, BLA, na ACA nke na-ahụ maka MPFC mata, ebe ọ bụ na Meth nwere ike imetụta àgwà mmekọahụ.

Nchọpụta dị ugbu a na omume mmekọahụ na nchịkwa nke Meth na-eme ka ọtụtụ ndị na-amụba na Nec, BLA, na ACA dị iche na nchọta site na nchọpụta ndị ọzọ na-egosi na ọnụ ọgụgụ dị iche iche nke ndị na-anọchite anya NAC na-akwalite ụgwọ ọrụ ọgwụ na ụgwọ ọrụ.

N'ụzọ doro anya, ọmụmụ nchọpụta electrophysiological nke tụnyere ntinye aka na nchịkwa nke oge na-achịkwa ụgwọ ọrụ (nri na mmiri) na cocaine na-egbuke egbuke egosiwo na nchịkwa nke cocaine na-arụ ọrụ dị iche iche, ndị na-adịghị na-ekpuchi ọnụ ọgụgụ ndị na-adịghị anabata n'oge omere na-anabata mmiri na nkwado nri (92%). Naanị 8% nke mkpokọta ụlọ ka egosipụtara site na cocaine na ụgwọ ọrụ nkịtị (Carelli et al., 2000).

N'adịghị iche, ọtụtụ (65%) nke cell na NAc gosipụtara ọrụ site na ụgwọ ọrụ dị iche iche (nri na mmiri), ọbụlagodi na otu onye na-eme ka ọ dịkwuo mma (sucrose) (Roop et al., 2002).

Otutu ihe nwere ike ime ka ha ghara inwe mmekorita na ugbua. Nke mbụ, a na-eji usoro nhazi dị iche iche eme ihe iji nyochaa arụmụmnta igwe. Ọmụmụ ihe nke ugbu a jiri usoro nyocha iji chọpụta nke mmemme na-eme ka ọ dị ọhụrụ site n'ụdị abụọ dị iche iche na-eme ka mmadụ abụọ na-ahụ maka immunocytochemisty maka Fos na PERK, na-enye ohere ka a nyochaa otu ịmalite ịmalite ịbanye n'otu ụbụrụ. N'ụzọ dị iche, nnyocha nke Carelli na ndị ọrụ ibe ha ji mee ihe ndekọ electrophysiological na-ejikọta na NAc nke ụmụ anụmanụ na-eme omume iji kwado ma nchịkọta onwe onye nke iji ọgwụ ọjọọ eme ihe na-eme ka otu sekit na-arụ ọrụ site na ụgwọ ọrụ nkịtị.

Nke abụọ, nchọpụta a na-amụ ugbu a na-enyocha ọdịiche dị iche iche nke okike, ya bụ, omume mmekọahụ na-atụle ọmụmụ ihe gara aga, nke ji nri na mmiri mee ihe na oke oke (Carelli, 2000). Nri na mmiri nwere ike ịba ụba karịa uru. Mmekọahụ na-akwụghachi ụgwọ dị ukwuu ma ụgbụ na-eme ka CPP gbanwee ngwa ngwa (Agmo na Berenfeld, 1990, Martinez na Paredes, 2001, Tenk, 2008). Ọ bụ ezie na oke oke ihe oriri na-eme CPP maka mmiri (Agmo et al., 1993, Klas na Clifton, 1997) na nri (Klas na Clifton, 1997), dAzu ndị na-adịghị mma na-eri ma na-ere CPP maka ihe oriri ndị ọzọ (Jarosz et al., 2006, Jarosz et al., 2007).

Nke atọ, ọmụmụ ihe anyị gụnyere ọgwụ ọjọọ dịgasị iche iche ma ọ bụrụ na e jiri ya tụnyere nchọpụta gara aga, iji methamphetamine na amphetamine kama cocaine. Ihe ndị na-apụta ugbu a na-egosi na Meth na Meter, ma ruo n'ókè amphetamine ka nta, mere ka ọ bụrụ na ọ bụ mmekorita na-arụ ọrụ. Ahụmahụ ọgwụ ọjọọ nwere ike ịbụ ihe kpatara ihe anyị chọpụtara. Umu ihe omumu nke di ugbu a jiri umu anu ndi enwere mmekorita nwoke na nwanyi, ma ogwu ojoo. N'ụzọ dị iche, nchọpụta electrophysiological banyere Carelli na ndị ọrụ ibe ha ji "anụmanụ a zụrụ azụ" nke natara ugboro ugboro na cocaine.

N'ihi ya, ọ ga-ekwe omume na meth na-ebido ịmalite nke ọkpụkpụ na-emegharị site na omume mmekọahụ na-agbanwe na ụmụ irighiri ọgwụ nwere ahụmahụ. Otú ọ dị, nchọpụta mbụ nke ụlọ nyocha anyị na-egosi na ahụike ọgwụ ọjọọ agaghị abụ isi ihe dịka omume mmekọahụ na omume Meth na ụmụ nwoke a na-emeso Meth na-emekọ ihe ọnụ dịka ndị na-aṅụ ọgwụ ọjọọ dịka akọwara ha n'ọmụmụ ihe ugbu a (20.3 ± 2.5% na NAc na 27.8 ± 1.3% na Nac shell; Frohmader na Coolen, ihe ndị a na-agbasabeghị).

N'ikpeazụ, nchọpụta a na-amụ ugbu a nyochaa ihe "kpọmkwem" nke ọgwụ ndị na-eji nlekọta na-agafe agafe. Ya mere, nyocha nke ugbu a anaghị ekpughe ozi banyere mpaghara ihe omimi nke na-achọ ma ọ bụ na-achọ ọgwụ na-ejikọta ụgwọ ọrụ ọgwụgwọ, kama nke ahụ na-ekpughe ọrụ nụ na-akpata site na ọgwụ pharmacological action of drug. N'ọmụmụ nchọpụta nke electrophysiological gara aga, ihe ndị na-emeghị ihe na-eme n'oge na-adịghị anya nke mmeghachi omume a gbadoro esiteghi na arụ ọrụ nke cocaine, kama ọ bụ ịdabere na ihe ndị na-akpakọrịta n'ime nchịkọta onwe onye (Carelli, 2000, Carelli, 2002). N'ụzọ doro anya, ọrụ nchịkwa NAc na-emetụta site n'igosipụta nkwalite nke onwe nke mmepụta ihe metụtara ikuku cocaine na intravenous nakwa dịka site na mgbatị aka (ntụgharị, ntinye ịpị) nke dị n'ime ihe omume a (Carelli, 2000, Carelli na Ijames, 2001, Carelli, 2002, Carelli na Wightman, 2004). Na nchịkọta, nchọpụta anyị maka nkwado site na nkwụsị nke mkpụrụ obi na ọgwụgwọ nwere ike ịbụ kpọmkwem maka ịmalite site n'inwe mmekọahụ ma na-enye Meth na Amph ọrụ.

Meth na mmekorita nwoke na nwanyi na-ekpuchi mmadu nke neurons na akuko NAc na ogwu na-adabere n'omume. Ngwá ọrụ na-arụ ọrụ na NAc nwere ike ikpuchi mmetụta Meth nwere ike inwe na mkpali na ụgwọ ọrụ na-akwụghachi ụgwọ nke omume mmekọahụ dịka ọnya nke NAc mebiri omume mmekọahụ (Liu et al., 1998, Kippin et al., 2004). Tụkwasị na nke a, ihe ndị a nwere ike ịchọta ebe a na-etinye ọgwụ mgbochi na ụbụrụ, n'ihi na Meth (1 mg / kg) dị ntakịrị belatara ọnụ ọgụgụ nke mkpụrụ ndụ abụọ ejiri na 50% tụnyere nchịkọta dị elu nke Meth (4 mg / kg). Ọ bụ ezie na ọmụmụ a akọwaghị phenotype kemịkị nke ụbụrụ na-arụkọ ọrụ, nchọpụta gara aga egosiwo na ọgwụ na-emetụta ọgwụ ọjọọ na okwu Fos na NAc dabere na dopamine (DA) na ndị na-enweta glutamate (Valjent et al., 2000, Ferguson et al., 2003, Valjent et al., 2005, Sun et al., 2008). Ọ bụ ezie na ọ bụghị ihe doro anya ma ọ bụrụ na ịmalite ịmalite ịmalite ime ihe na NC na-adabere na ndị a nabatara, a gosipụtawo ya na mpaghara ụbụrụ ndị ọzọ,Lumley na Hull, 1999, Dominguez et al., 2007). THus, Meth nwere ike ime ihe na-eme ka ọ na-arụ ọrụ mgbe ọ na-enwe mmekọahụ site na ịmepụta dopamine na ndị na-anabata glutamate. Ọrụ nke NAc glutamate na-enwe mmekọahụ bụ ugbu a doro anya, ma ọ bụ nke ọma guzobere na DA na-arụ ọrụ dị oké mkpa na mkpali maka omume mmekọahụ (Hull et al., 2002, Hull et al., 2004, Pfaus, 2009). Ihe omuma nke microdialysis na-ebute abawanye na NAc DA efflux n'oge mmekorita na mmekorita nke omume nwoke na nwanyi (Fiorino na Phillips, 1999a, Lorrain et al., 1999) na ọgwụ na-eme ka mesolimbic DA efflux gbakwunyere na mmezi nke nbido na mmezi nke ịkpa mmekọahụ (Pfaus na Everitt, 1995). Ọzọkwa, ọmụmụ nchọpụta NDI na-egosi NDỊ na-alụ ọgụ na NAc na-egbochi inwe mmekọahụ, mgbe agonists na-akwalite nkwalite mmekọahụr (Everitt et al., 1989, Pfaus na Phillips, 1989). Ya mere, Meth nwere ike imetụta mkpali maka mmekorita nwoke na nwanyi site na ịbanye n'aka ndị nabatara ya.

N'adịghị ka NAc, ọnụọgụ abụọ sel abụọ a na-akpọ na BLA na ACA nọgidere na-agbanwe agbanwe n'enweghị mgbanwe ọ bụla n'agbanyeghị Meth. BLA di oke nkpa maka ihe omuma nke ndi na-adighi nma ma tinye aka n'enye ihe nkwado na ugwo onu ugwo mgbe o na -Everitt et al., 1999, Cardinal et al., 2002, Hụ, 2002). BLA laioned oke gosiri nbelata leba ịpị maka conditioned stimuli paired na nri (Everitt et al., 1989) ma ọ bụ inwe mmekọahụ (Everitt et al., 1989, Everitt, 1990). N'ụzọ dị iche, nchịkwa a anaghị emetụta usoro nke nri na ịkpa mmekọahụ (Cardinal et al., 2002). BLA na-ekerekwa òkè dị ukwuu na icheta ihe ndị na-emetụta ọnọdụ ọgwụ ọjọọ (Grace na Rosenkranz, 2002, Laviolette na Grace, 2006). Ọrịa ma ọ bụ ihe ndị na-emepụta ọgwụ na-adịghị na BLA gbochie nnweta (Whitelaw et al., 1996) na okwu (Grimm na Lee, 2000) ịnabataghachi cocaine nwere nkwonkwo, ebe ọ na-adịghị emetụta usoro ọgwụgwọ ọgwụ. Ọzọkwa, Amph na-etinye aka ozugbo n'ime ihe ndị na-ebute BLA n'ime ntinye ọgwụ ọjọọ nwere ike ịmaliteghachi n'ihu ọnụnọ ahụ (Lee et al., 2003). Ya mere, ọ ga-ekwe omume na psychostimulant-enwekwukwa na nnyefe na BLA utịp na-enwe mmetụta nke mmetụta uche na ịchọ (Ledford et al., 2003) nke ụgwọ ọrụ ego, si otú ahụ na-enye aka n'ịgbagharị agụụ mmekọahụ na ọchịchọ ndị Meth kwuru (Semple et al., 2002, Green na Halkitis, 2006).

Na ACA, ntinye aka nke ụmụ nwoke na-ahụ maka mmekọahụ na-edozi ahụ-onwe ya na nke Meth, ebe ọ bụ na ejighị Amph. Ọ bụ ezie na Meth na Amph nwere ihe ndị dị otú ahụ na ụlọ ọgwụ, Meth bụ ikike nke psychostimulant karịa Amph nke nwere mmetụta na-adịgide adịgide (NIDA, 2006). Nnyocha nke Goodwin et al. gosiri na Meth na - emepụta ihe karịrị DA efflux ma na - egbochi nkwụsị nke ndị na - eji ya eme ihe n'ụzọ dị irè karị na rat NAc karịa Amph. Ihe ndị a nwere ike inye aka na ihe ndị na-eri ahụ nke Meth ma tụnyere Amph (Goodwin et al., 2009) nakwa ma eleghị anya, esemokwu dị iche iche na-eme ka ọkpụkpụ dị iche iche dị n'etiti ọgwụ abụọ ahụ. Otú ọ dị, ọ bụghị ihe doro anya ma usoro dịgasị iche iche nke nsonaazụ ọ bụ n'ihi ọdịiche dị iche iche dị n'etiti ọgwụ ọjọọ ma ọ bụ ihe isi ike metụtara metụtara doses n'ọrụ na ịchọ nyocha ọzọ.

Meth na nwoke na nwanyi enweghi mmekorita na mpaghara ndi ozo nke mPFC (IL na PL). Na oke ahụ, a na-amụrụ ACA ọtụtụ ihe site na iji ọrụ ndị na-akpali agụụ mmekọahụ, na-akwado ọrụ dị na mkpakọrịta na-akpali akpali (mkpakọrịta na-Everitt et al., 1999, Hụ, 2002, Cardinal et al., 2003). Enwere otutu ihe akaebe na ndị MPFC na-etinye aka n'ịṅụ ọgwụ ọjọọ na nlọghachi azụ n'omume ọgwụ na ịṅụ ọgwụ ọjọọ ma ụmụ mmadụ ma oke (Grant et al., 1996, Childress et al., 1999, Capriles et al., 2003, McLaughlin na Lee, 2003, Shaham et al., 2003, Kalivas na Volkow, 2005). Mn linea na nke a, e kwuwo na mPFC dysfunctioning kpatara site na ugboro ugboro na-egosi na ọgwụ ọjọọ eme ihe nwere ike ibu ọrụ nke ịchịkwa ikike mkpesa na omume ndị na-eduzi ọgwụ ọjọọ dị ka e kwuru na ọtụtụ ndị na-eri ahụ (Jentsch na Taylor, 1999). Ihe omuma ndi ozo site na laabu anyi gosiputara na mpo nke mPFC na-eme ka a na-acho ime ihe gbasara mmekorita nke nwanyi mgbe enwere ya na ihe mkpali (Davis et al., 2003). Ọ bụ ezie na nchọpụta a emeghị nchọpụta banyere ACA, ọ na-akwado nkwupụta ahụ na mPFC (na ACA) na-akwado mmetụta nke Meth na nkwụsị nke ịchịkwa njide ejidere mmekọahụ dị ka akụkọ Meth na-akọ (Salo et al., 2007).

N'ikpeazụ, ọmụmụ ihe ndị a na-emepụta nzọụkwụ dị oke mkpa iji ghọtakwuo otú iji ọgwụ ọjọọ eme ihe n'ụzọ okporo ụzọ nke na-emekarị ka ọ bụrụ ụgwọ ọrụ. Ọzọkwa, nchọpụta ndị a na-egosi na n'adịghị ka nkwenkwe dị ugbu a na ọgwụ ọjọọ eme ihe adịghị arụ ọrụ n'otu sel ahụ n'ime usoro mesolimbic dịka ụgwọ ọrụ nkịtị, Meth, na n'obere ogo Amph, mee ka otu mkpụrụ ndụ dị ka omume mmekọahụ. N'aka nke ya, ndị a na-arụ ọrụ na-eme ka ha nwee ike ịchọta ịchọta ụgwọ ọrụ nkịtị na-esochi ọgwụ ọjọọ. N'ikpeazụ, ihe ọmụmụ nke ọmụmụ a nwere ike itinye aka na nghọta anyị banyere ndabere nke ịṅụ ọgwụ ọjọọ n'ozuzu. Nkọwa nke ọdịdị na iche iche, nakwa ngbanwe nke mmechi nke usoro mesolimbic nke omume rụrụ arụ na-eme ka a ghọtakwuo mmebi ahụ na mgbanwe ndị ọzọ na ụgwọ ọrụ.

Nkweta

A na-akwado nyocha a site na nkwado sitere n'aka National Institute of Health R01 DA014591 na Ụlọ Ọrụ Nlekọta Ahụ Ike nke Canada RN 014705 gaa LMC.

AHỤ

  • ABC
  • avidin-biotin-horseradish peroxidase mgbagwoju
  • ACA
  • ebe a na-agbanye aka
  • Amph
  • d-amphetamine
  • BLA
  • amygdala
  • BNSTpl
  • ihe omuma nke ihe omimi nke stria terminalis
  • BNSTpm
  • oghere bedromedial bed nke stria terminalis
  • BT
  • biotinylated tyramide
  • CeA
  • centin amygdala
  • CPP
  • ebe nchekwa ebe
  • E
  • ejaculation
  • EL
  • Ejaculation adịghị mma
  • IF
  • mpaghara infralimbic
  • IL
  • nkwụsị na-emepụta ihe
  • IM
  • intromission
  • M
  • ugwu
  • MAP Kinase
  • mitogen-activated protein kinase
  • MEApd
  • posterodorsal medial amygdala
  • Meth
  • methamphetamine
  • ML
  • eriri ugwu
  • mPFC
  • cortex prefrontal medial
  • MPN
  • oghere preoptic medial
  • NAc
  • nuwanye Accumbens
  • PB
  • nchekwa phosphate
  • PBS
  • saline na-enye phosphate
  • PEI
  • post ejaculatory oge
  • kwuo
  • phosphorylated MAP Kinase
  • PL
  • mpaghara mbụ
  • VTA
  • mpaghara ọnụ ọgụgụ dị iche iche

Ihe odide ala

Nkwupụta Nkwupụta Onye Nkwusa: Nke a bụ faịlụ PDF nke ihe odide a na-akwadoghị nke akwadora maka mbipụta. Dịka ọrụ nke ndị ahịa anyị, anyị na-enye nsụgharị mbụ nke ihe odide ahụ. Ihe odide a ga-enwe ngbanwe, nhazi, na nyochaa ihe kpatara ya tupu e bipụ ya na nke ikpeazụ ya. Biko rịba ama na n'oge mmepụta usoro njehie nwere ike ịchọta nke nwere ike imetụta ọdịnaya ahụ, ihe niile gbasara iwu na-emetụta akwụkwọ akụkọ ahụ.

References

  1. Agmo A. Nwoke oke nwoke na nwanyi. Ogwe Brain Res Brain Res Brain Res. 1997; 1: 203-209. [PubMed]
  2. Agmo A, Berenfeld R. Ịghaghachi ihe onwunwe nke ejaculation na oke oke: ọrụ nke opioids na dopamine. Behav Neurosci. 1990; 104: 177-182. [PubMed]
  3. Agmo A, Federman I, Navarro V, Padua M, Velazquez G. Ụgwọ na mmesi ike nke mmiri na-emepụta: Ọrụ nke opioids na subdompes nyocha dopamine. Pharmacol Biochem Behav. 1993; 46 [PubMed]
  4. Balfour ME, Yu L, Coolen LM. Mmekọahụ na ihe gbasara gburugburu ebe obibi na-eme ka usoro nke mesolimbic dị na oke ụmụ nwoke. Neuropsychopharmacology. 2004; 29: 718-730. [PubMed]
  5. Baum MJ, Everitt BJ. Nkọwa ka ukwuu nke c-fos na mpaghara preoptic na-ahụ anya mgbe ejiri alụlụlụ na-arụ ọrụ: Nrụnye ntinye ntinye sitere na amygdala na midbrain etiti etiti. Neuroscience. 1992; 50: 627-646. [PubMed]
  6. Capriles N, Rodaros D, Sorge RE, Stewart J. Otu ihe na-eme maka nrụrụ mbụ na nrụgide - na cocaine na-ebido ịmaliteghachi ịchọta cocaine na oke. Psychopharmacology (Berl) 2003; 168: 66-74. [PubMed]
  7. Cardinal RN, Parkinson JA, Hall J, Everitt BJ. Mmetụta na mkpali: ọrụ nke amygdala, ventral striatum, na cortex prefrontal. Neuroscience & Biobehavioral Nyocha. 2002; 26: 321–352. [PubMed]
  8. Cardinal RN, Parkinson JA, Marbini HD, Toner AJ, Bussey TJ, Robbins TW, Everitt BJ. Ọrụ nke cingulate cortex na-achịkwa omume site Pavlovian conditioned stimuli na oke. Neuroscience Ọbụrụ. 2003; 117: 566-587. [PubMed]
  9. Carelli RM. Mmegharị nke ụbụrụ accumbens na-emepụta site na nkwalite ndị metụtara cocaine n'oge nnyefe onwe onye. Synapse. 2000; 35: 238-242. [PubMed]
  10. Carelli RM. Nucleus na-ebuwanye igba egbe cell n'oge ebumnuche ebumnuche maka cocaine vs. 'eke' mkwado. Ahụike & Àgwà. 2002; 76: 379–387. [PubMed]
  11. Carelli RM, Ijames SG. Nhọrọ nke a na-ejikọta nke eriri ndị na-eme ka cocaine pụta na oge oge otutu mmiri / cocaine. Research Brain. 2001; 907: 156-161. [PubMed]
  12. Carelli RM, Ijames SG, AJ. Ihe akaebe na ikewapụta ihe dị iche iche na gburugburu ebe obibi na-eme ka cocaine gbanwee na ụgwọ ọrụ "mmiri" (mmiri na nri). J Neurosci. 2000; 20: 4255-4266. [PubMed]
  13. Carelli RM, Wightman RM. Igwe microcircuitry na-arụ ọrụ n'ime ọgwụ ọjọọ riri nne: ihe ọmụma sitere na njirimara oge na-egosi n'oge omume. Nyocha a na-eme ugbu a na Neurobiology. 2004; 14: 763-768. [PubMed]
  14. Carelli RM, Wondolowski J. Selective encoding of cocaine with natural rewards by nucleus accumbens neurons enweghi ihe jikọrọ ya na ọgwụ na-adịghị ala ala. J Neurosci. 2003; 23: 11214-11223. [PubMed]
  15. Chang JY, Zhang L, Janak PH, Woodward DJ. Nzaghachi nke Neuronal na cortex na-ebu ụzọ na-ebuwanye ibu n'oge heroin na-elekọta onwe ya na mkpịsị ụkwụ na-enweghị isi. Nkwụsị Brain. 1997; 754: 12-20. [PubMed]
  16. Chen BT, Mbụ Bowers MS, Martin M, Hopf FW, Guillory AM, Carelli RM, Chou JK, Bonci A. Cocaine ma ọ bụghị Ụgwọ Ngwá Ọrụ Nlekọta Onwe onye ma ọ bụ Pasina Cocaine Infusion Na-emepụta LTP na-aga n'ihu na VTA. Neuron. 2008; 59: 288-297. [PMC free article] [PubMed]
  17. Chen PC, Chen JC. Ọrụ Cdk5 dịwanye mma na P35 Translocation na Ventral Striatum nke Nnukwu Methamphetamine-Na-emeso Rats. Neuropsychopharmacology. 2004; 30: 538-549. [PubMed]
  18. Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O'Brien CP. Ọbịbịa na-arụ ọrụ nke ọma mgbe a na-achọ cocaine. Am J Ọchịachukwu. 1999; 156: 11-18. [PMC free article] [PubMed]
  19. Choe ES, Chung KT, Mao L, Wang JQ. Amphetamine enwekwu phosphorylation nke procellular signal-regulated kinase na transcript ihe na oke striatum site otu m metabotropic glutamate natara. Neuropsychopharmacology. 2002; 27: 565-575. [PubMed]
  20. Choe ES, Wang JQ. CaMKII na-achịkwa ERK1 / 2 phosphorylation nke amphetamine n'ime eriri. Neuroreport. 2002; 13: 1013-1016. [PubMed]
  21. Davis JF, Loos M, Coolen LM. Society maka Neuroendocrinology nke Behavioral. Vol. 44. Cincinnati, Ohio: Hormones na Omume; 2003. Mkpịsị nke cortex na-ahụ maka ọdịmma ahụ adịghị emebi omume mmekọahụ na oke ụmụ nwoke; p. 45.
  22. Di Chiara G, Imperato A. Ọgwụ ọjọọ ndị ụmụ mmadụ na-emejọ na-eme ka synaptic na-eme ka concentros concentrations na usoro mesolimbic nke na-agagharị na oke. Proc Natl Acad Sci US A. 1988; 85: 5274-5278. [PMC free article] [PubMed]
  23. Dominguez JM, Balfour ME, Lee HS, Brown HJ, Davis BA, Coolen LM. Mmekọrịta na-eme ka ndị na-anabata NMDA na mpaghara preoptic na-atụgharị uche nke oke oke. Neuroscience Ọbụrụ. 2007; 121: 1023-1031. [PubMed]
  24. Elifson KW, Klein H, Sterk CE. Ndị na-ede akwụkwọ banyere inwe mmekọahụ n'ihe gbasara ndị ọrụ ọgwụ ọjọọ. Nyocha akụkọ banyere mmekọahụ. 2006; 43: 318-327. [PubMed]
  25. Ellkashef A, Vocci F, Hanson G, White J, Wickes W, Tiihonen J. Pharmacotherapy nke Methamphetamine Ịṅụ ọgwụ ọjọọ: Mmelite. Mmetụta Mmebi. 2008; 29: 31-49. [PMC free article] [PubMed]
  26. Everitt BJ. Mkpali mmekorita: nyocha ihe omumu na nke omume nke usoro ihe ngbagha nke ndi nwoke. Neurosci Biobehav Mkpuchi 1990; 14: 217-232. [PubMed]
  27. Everitt BJ, Cador M, Robbins TW. Mmekọrịta dị n'agbata amygdala na ventral striatum na mkparịta ụka na-akpali akpali: Studies na-eji usoro nke abụọ nke nkwado mmekọahụ. Neuroscience. 1989; 30: 63-75. [PubMed]
  28. Everitt BJ, Fray P, Kostarczyk E, Taylor S, Stacey P. Nnyocha nke omume aka na inwe mmekọahụ na-akwado ụmụ nwoke (Rattus norvegicus): I. Na-ejikwa nlezianya na-ahụ ihe nkiri na-anabata nwanyi. J Comp Psychol. 1987; 101: 395-406. [PubMed]
  29. Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW. Mmekorita ndi otu na-eri ihe na mmekorita nke oru Amygdala-Ventral Striatal Subsystems. Akwụkwọ akụkọ nke New York Academy of Sciences. 1999; 877: 412-438. [PubMed]
  30. Everitt BJ, Stacey P. Nyocha nke omume aka na inwe nkwado nwoke na nwanyị (Rattus norvegicus): II. Mmetụta nke ọnya ndị preoptic, castration, na testosterone. J Comp Psychol. 1987; 101: 407-419. [PubMed]
  31. Feltenstein MW, Lee RE. Neurocircuitry nke riri ahụ: nkọwa. Br J Pharmacol. 2008; 154: 261-274. [PMC free article] [PubMed]
  32. Ferguson SM, Norton CS, Watson SJ, Akil H, Robinson TE. Okwu mRNA chosamine na-eme ka a na-eme ihe na-eme ka ọ bụrụ ihe na-akpata: mmetụta nke DA na onye na-anabata ihe NMDA na-agbanwe dịka ọrụ nke phenotype na nụ gburugburu ebe obibi. Akwụkwọ Neurochemistry. 2003; 86: 33-44. [PubMed]
  33. Fiorino DF, Coury A, Phillips AG. Mgbanwe dị iche iche na-agbanwe na ngwongwo na-eme ka efflux dopamine n'oge mmetụta Coolidge na oke oke. J Neurosci. 1997; 17: 4849-4855. [PubMed]
  34. Fiorino DF, Phillips AG. Mmezi nke Mmekọahụ na Ọganihu Efflux Na-amụbawanye na Nkọwa Na-ahụ Maka Ọkpụkpụ Na-ahụ Maka Ọkpụkpụ Na-ahụ Maka Ọmụmụ D-Amphetamine. J Neurosci. 1999a; 19: 456-463. [PubMed]
  35. Fiorino DF, Phillips AG. Inye mmekorita nwoke na nwanyi n'adiri nwoke na nwanyi na-eso amititamine na-emetụta ihe omume. Psychopharmacology. 1999B; 142: 200-208. [PubMed]
  36. Goodwin JS, Larson GA, Swant J, Sen N, Javitch JA, Zahniser NR, De Felice LJ, Khoshbouei H. Amphetamine na Methamphetamine Na-emetụta Dopamine Transporters na Vitro na Vivo. J Biol Chem. 2009; 284: 2978-2989. [PMC free article] [PubMed]
  37. Grace AA, Rosenkranz JA. Iwu nke nzaghachi nke ọnọdụ amygdala neuron. Ahụike & Àgwà. 2002; 77: 489–493. [PubMed]
  38. Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS, Margolin A. Ịrụ ọrụ nke ihe nchekwa ebe a na-achọpụta ihe na-achọ cocaine. Proc Natl Acad Sci US A. 1996; 93: 12040-12045. [PMC free article] [PubMed]
  39. Green AI, Halkitis PN. Crystal methamphetamine na mmekọrịta mmekọrịta nwoke na nwanyị na subculture gay: Omenala, Ahụike na Mmekọahụ. 2006; 8: 317–333. [PubMed]
  40. Grimm JW, Lee RE. Nkwụsị nke ọdịbụrụ limbic nu na nke abụọ na-akwụghachi ụgwọ dị na anụmanụ nke nlọghachi azụ. Neuropsychopharmacology. 2000; 22: 473-479. [PubMed]
  41. Mkpụrụ EM, Lorrain DS, Du J, Matuszewich L, Lumley LA, Putnam SK, Moses J. Hormone-neurotransmitter na-emekọ ihe n'ịchịkwa mmekọahụ. Nnyocha Research Brain. 1999; 105: 105-116. [PubMed]
  42. Hull EM, Meisel RL, Sachs BD. Omume nwoke na nwanyi. Na: Pfaff DW, et al., Editọ. Ụbụrụ Hormones na Ahụmume. San Diego, CA: Elsevier Science (USA); 2002. 1-138.
  43. Hull EM, Muschamp JW, Sato S. Dopamine na serotonin: mmetụta na omume nwoke na nwanyị. Ahụike & Àgwà. 2004; 83: 291–307. [PubMed]
  44. Akwara K, Nitta A, Mizoguchi H, Mohri A, Murai R, Miyamoto Y, Noda Y, Kitaichi K, Yamada K, Nabeshima T. Mmetụta nke nchịkwa otu na ugboro ugboro nke methamphetamine ma ọ bụ morphine na etutoglycan C na mkpụrụ ụbụrụ rat. Akwụkwọ bụ International Journal of Neuropsychopharmacology. 2006; 9: 407-415. [PubMed]
  45. Jarosz PA, Kessler JT, Sekhon P, Coscina DV. Ebe mmasị dị mma (CPPs) na "nri nri nri" dị elu na ụbụrụ na-edozi ahụ na-edozi ahụ maka ibu ibu: Nguzogide mgbochi naltrexone. Usoro ọgwụ na ọgwụ nje na ọgwụ. 2007; 86: 699-704. [PubMed]
  46. Jarosz PA, Sekhon P, Coscina DV. Mmetụta nke ịkwado ihe opioid na-etinye ọnọdụ maka nri oriri. Usoro ọgwụ na ọgwụ nje na ọgwụ. 2006; 83: 257-264. [PubMed]
  47. Jentsch JD, Taylor JR. Mbipu nke na-esi na mbido na-emebiga ihe ókè na iji ọgwụ ọjọọ eme ihe: ihe na-egosi nchịkwa omume site na nkwalite nke ụgwọ ọrụ. Psychopharmacology (Berl) 1999; 146: 373-390. [PubMed]
  48. Kalivas PW, Volkow ND. Ihe na-eme ka ọ bụrụ ihe na-adịghị mma: ụdị ọgwụgwọ nke mkpali na nhọrọ. Am J Ọchịachukwu. 2005; 162: 1403-1413. [PubMed]
  49. Kelley AE. Nchekwa na ụtaba: na-ekerịta sekit na-ekpo ọkụ na usoro ikuku. Neuron. 2004; 44: 161-179. [PubMed]
  50. Kippin TE, Sotiropoulos V, Badih J, Pfaus JG. Ọrụ ndị na-emegiderịta onwe ha nke ngwongwo ahụ na-ebuwanye ibu na akụkụ hypothalamic mpụta ihu na-achịkwa omume mmekọahụ na oke nwoke. European Journal of Neuroscience. 2004; 19: 698-704. [PubMed]
  51. Laviolette SR, Grace AA. Cannabinoids Mmetụta Mmetụta Na-emetụta Ọmụmụ Ihe ntanetị na Neurons nke Medial Prefrontal Cortex site na Ntinye Ntinye Amygdala. J Neurosci. 2006; 26: 6458-6468. [PubMed]
  52. Ledford CC, Fuchs RA, Lee RE. Nweghachi ike ịmalite ịchọta Cocaine-Na-achọ Omume Mgbe D-amphetamine Infusion banye na Blateralral Amygdala. Neuropsychopharmacology. 2003; 28: 1721-1729. [PubMed]
  53. Lett BT. Mgbasaa ugboro ugboro na-esiwanyewanye ike kama iwepụ mmetụta na-akwụghachi ụgwọ nke amphetamine, morphine, na cocaine. Psychopharmacology (Berl) 1989; 98: 357-362. [PubMed]
  54. Liu YC, Sachs BD, Salamone JD. Mmekorita nwoke na nwanyi na-enweghi mmekorita nke nwoke ma obu nwanyi na-enweghi nsogbu. Pharmacol Biochem Behav. 1998; 60: 585-592. [PubMed]
  55. Lorrain DS, Riolo JV, Matuszewich L, Hull EM. Serotonin Hypothalamic Na-eme N'ikpeazụ Na-egbochi Mmetụta Na-eme Ka Ahụhụ Dọkọọ: Ihe Ndị Na-akpata Mmekọahụ. J Neurosci. 1999; 19: 7648-7652. [PubMed]
  56. Lumley LA, Hull EM. Mmetụta nke antagonist D1 na nke ahụmahụ mmekọahụ na-achịkwa-emetụta Fos-dị ka nkwụnyeghị aka n'ime oghere preoptic medial. Research Brain. 1999; 829: 55-68. [PubMed]
  57. Martinez M, Paredes RG. Naanị ịlụ di na nwunye na-enye ụgwọ ọrụ na oke nke ma nwoke ma nwanyị. Ọrịa ọjọọ. 2001; 40: 510-517. [PubMed]
  58. McLaughlin J, Lee RE. Idozi mmechi nke cortex mbụ na dorsomedial na amygdala nke na-ezughị okè na-eme ka ndị mmadụ nwetaghachi ihe omume cocaine na-achọ ka ha kwụsị. Psychopharmacology (Berl) 2003; 168: 57-65. [PubMed]
  59. Mitchell JB, Stewart J. Ịmalite ịkpa àgwà nwoke na nwanyi na ụbụrụ tupu enwere mmekorita nke mbụ na-ejikọta ya na nchịkwa nke morphine. Usoro ọgwụ na ọgwụ nje na ọgwụ. 1990; 35: 367-372. [PubMed]
  60. Mizoguchi H, Yamada K, Mizuno M, Mizuno T, Nitta A, Noda Y, Nabeshima T. Ụgwọ Ngwá Ụgwọ Methamphetamine site na Extracellular Signal-Regulated Kinase 1 / 2 / ets-Dị ka Gene-1 na-egosi Ụzọ site na Ntinye nke Nkọwa NIDA ( Nyocha akụkọ: Mmegbu na ọgwụ nchịkwa na-emetụta methamphetamine 2006 NIH Nkọwapụta 06-4210. [PubMed]
  61. Perks SM, Clifton PG. Ntughari nyocha na mmasị ebe. Ahụike & Àgwà. 1997; 61: 1–5. [PubMed]
  62. Pfaus JG. Ụzọ nke agụụ mmekọahụ. Journal of Sexual Medicine. 2009; 6: 1506-1533. [PubMed]
  63. Pfaus JG, Everitt BJ. The psychopharmacology nke omume mmekọahụ. Na: Bloom FE, Kupfer DJ, editọ. Psychopharmacology: ọgbọ nke anọ ọganihu. New York: Ugo; 1995. 743-758.
  64. Pfaus JG, Heeb MM. Mmetụta nke Ọmịiko Na-amalite n'oge na-adị na Brain Mgbe Mkparịtaahụ Mmekọahụ nke Ndị Nwanyi na Ụmụ Mkpanaka. Bulletin Research Brain. 1997; 44: 397-407. [PubMed]
  65. Pfaus JG, Kippin TE, Centeno S. Ịdị nro na omume mmekọahụ: nyochaa. Ọrịa ọjọọ. 2001; 40: 291-321. [PubMed]
  66. Pfaus JG, Phillips AG. Mmetụta dị iche iche nke onye na-anabata dopamine na-eme ka àgwà nwoke na nwanyị nwee mmekọahụ. Psychopharmacology. 1989; 98: 363-368. [PubMed]
  67. Pierce RC, Kumaresan V. Usoro mesolimbic dopamine: Thezọ ikpeazụ kachasị mma maka mmetụta ume nke ọgwụ ọjọọ? Neuroscience & Biobehavioral Nyocha. 2006; 30: 215–238. [PubMed]
  68. Pitchers KK, Balfour ME, Lehman MN, Richtand NM, Yu L, Coolen LM. Mmekọahụ na-ebute usoro plasticity n'ime usoro mesolimbic. Nyocha Ọrịa. 2009 Na pịa.
  69. Ranaldi R, Pocock D, Zereik R, Amamihe. Mgbanwe a na-enweta na ngwoputa nke na-emepụta ihe na-eme ka ọ dị njọ n'oge mmezi, ikpochapu, na ntinyeghachi nke nchịkwa onwe-ahụ nke D-amphetamine. J Neurosci. 1999; 19: 4102-4109. [PubMed]
  70. Rawson RA, Washton A, Domier CP, Reiber C. Ọgwụ ọjọọ na mmetụta mmekọahụ: ọrụ nke ụdị ọgwụ na okike. Ndekọ ọgwụgwọ. 2002; 22: 103-108. [PubMed]
  71. Robertson GS, Pfaus JG, Atkinson LJ, Matsumura H, Phillips AG, Fibiger HC. Mmekọahụ na-eme ka okwu c-fos pụta n'ọnụ n'ọdịnihu nke oke nwoke. Nkwụsị Brain. 1991; 564: 352-357. [PubMed]
  72. Roop RG, Hollander RJ, Carelli RM. Na-emewanye ihe na-eme n'oge a otutu oge maka mmiri na sucrose mmesi ike na oke. Synapse. 2002; 43: 223-226. [PubMed]
  73. Salo R, Nordahl TE, Natsuaki Y, Leamon MH, Galloway GP, Mmiri C, Moore CD, Buonocore MH. Njikwa Ntị na Mkpụrụ Metabolite Brain na Abusers Methamphetamine. Nyocha Ọrịa. 2007; 61: 1272-1280. [PubMed]
  74. Schilder AJ, Lampinen TM, Miller ML, Hogg RS. Crystal methamphetamine na ecstasy dị iche na mmekọrita nwoke na nwanyị na-eto eto. Akwụkwọ akụkọ Canada nke ahụike ọha na eze. 2005; 96: 340-343. [PubMed]
  75. Lee RE. Mkpụrụ akụkụ ndị ọzọ nke nlọghachi na-agwọ ọrịa na-achọ omume ọgwụ ọjọọ. Usoro ọgwụ na ọgwụ nje na ọgwụ. 2002; 71: 517-529. [PubMed]
  76. Hụ RE, Fuchs RA, Ledford CC, McLaughlin J. Drug Addiction, Relapse, na Amygdala. Akwụkwọ akụkọ nke New York Academy of Sciences. 2003; 985: 294-307. [PubMed]
  77. Semple SJ, Patterson TL, Grant I. Ihe mkpali ndị metụtara na methamphetamine n'etiti ndị ikom HIV ndị nwere mmekọahụ na ụmụ nwoke. Ndekọ ọgwụgwọ. 2002; 22: 149-156. [PubMed]
  78. Shaham Y, Shalev U, Lu L, De Wit H, Stewart J. Ụdị nlọghachite nke nlọghachi azụ ọgwụ: akụkọ ihe mere eme, usoro na nchọpụta dị ukwuu. Psychopharmacology (Berl) 2003; 168: 3-20. [PubMed]
  79. Shippenberg TS, Heidbreder C. Nchọpụta ihe na-enye ụgwọ ọrụ nke cocaine: àgwà ndị na-emepụta ọgwụ na nke anụ ahụ. J Pharmacol Exp Ther. 1995; 273: 808-815. [PubMed]
  80. Shippenberg TS, Heidbreder C, Lefevour A. Mmetụta uche na mmetụta dị mma nke morphine: ọgwụ na azụmapụ. Eur J Pharmacol. 1996; 299: 33-39. [PubMed]
  81. Somlai M, Kelly JA, McAuliffe TL, Ksobiech K, Hackl KL. Ndị na-ekwu banyere ụdị mmekọahụ ndị na-ebute mmekọahụ na HIV na-egosi na ndị ikom na ndị inyom na-aṅụ ọgwụ ọjọọ. Ọrịa AIDS na àgwà. 2003; 7: 383-393. [PubMed]
  82. Mmiri nke A, Peters R, Shegog R, White D, Kelder S. Nleta Methamphetamine na Mmetụta Mmekọahụ Mmezi na Ụmụ akwụkwọ Ọchịchị High School na United States: Nchoputa site na Nyocha Ebumnuche nke Ọchịchị. Science Science. 2007; 8: 103-113. [PubMed]
  83. Sun WL, Zhou L, Hazim R, Quinones-Jenab V, Jenab S. Mmetụta dopamine na NMDA natara na cocaine-emebata Fos okwu na striatum nke Fischer oke. Research Brain. 2008; 1243: 1-9. [PMC free article] [PubMed]
  84. Swanson LW, nchịkọta akụkọ. Map nke Brain: Ụdị nke Bra Bra. Amsterdam: Elsevier Science; 1998.
  85. Tenk CM, Wilson H, Zhang Q, Pitchers KK, Coolen LM. Ụgwọ mmekọahụ na oke nwoke: Mmetụta nke ahụmahụ mmekọahụ na ọnọdụ ebe a na-atụkarị anya na ejaculations na intromissions. Ọrịa ọjọọ. 2008 [PMC free article] [PubMed]
  86. Valjent E, Corvol JC, Peeji nke C, Besson MJ, Maldonado R, Caboche J. Ịnweta ihe mgbakwunye mgbazigharị na-edozi mkpụrụ ndụ nke cocaine na-akwụ ụgwọ. J Neurosci. 2000; 20: 8701-8709. [PubMed]
  87. Valjent E, Peeji nke C, Herve D, Girault JA, Caboche J. Ndị omekorita na ọgwụ ndị na-adịghị eri ahụ na-emepụta ihe dị iche iche na nke a kapịrị ọnụ nke mmeghe ERK na ụbụrụ ụbụrụ. Eur J Neurosci. 2004; 19: 1826-1836. [PubMed]
  88. Valjent E, Pascoli V, Svenningsson P, Paul S, Enslen H, Corvol JC, Stipanovich A, Caboche J, Lombroso PJ, Nairn AC, Greengard P, Herve D, Girault JA. Iwu nke protein phosphatase cascade na-enye ohere ka convergent dopamine na glutamate na-egosi ịrụ ọrụ ERK na striatum. Proc Natl Acad Sci US A. 2005; 102: 491-496. [PMC free article] [PubMed]
  89. Vanderschuren LJ, Kalivas PW. Ngbanwe dị na dopaminergic na glutamatergic nnyefe n'ime ntinye na nkwupụta nke nhazi ihe omume: nlezianya dị oké njọ nke ọmụmụ ihe kpọmkwem. Psychopharmacology (Berl) 2000; 151: 99-120. [PubMed]
  90. Lee JG, Coolen LM. Ịmalite ịmalite ịmalite mmekọahụ na ụbụrụ ụbụrụ nwoke na nwanyị. Nnyocha Research Brain. 1998; 92: 181-193. [PubMed]
  91. Whitelaw RB, Markou A, Robbins TW, Everitt BJ. Ọrịa na-enweghị atụ nke amygdala na-enweghị ihe ọ bụla na-eme ka ọ ghara ịdị na-achọ omume ịchọ mma cocaine n'okpuru usoro mgbakọ nke abụọ. Psychopharmacology. 1996; 127: 213-224. [PubMed]
  92. Onye maara ihe. Ọrịa na-eri ahụ. Nyocha a na-eme ugbu a na Neurobiology. 1996; 6: 243-251. [PubMed]