Ịhapụ ịba ụra, ịbanye na nri na-edozi ahụ na-ebute omume ndakpọda mmụọ na mkpị na-eri nri (2012)

Behav Pharmacol. Akwụkwọ edemede; dị na PMC 2014 Feb 25.

Behav Pharmacol. 2012 Sep; 23 (0): 593–602 .

doi: 10.1097 / FBP.0b013e328357697f

PMCID: PMC3934429

NIHMSID: NIHMS554308

Attilio Iemolo,a,b,* Marta Valenza,a,b,c,* Lisa Tozier,b Clifford M. Knapp,b Conan Kornetsky,b Luca Steardo,dValentina Sabino,a,b and Pietro Cottonea, b

nkịtị

Mmụba nnweta nri ndị na-atọ ụtọ nke ukwuu bụ isi ihe na-enye aka na mmepe nke iri ihe ike na oke ibu na nsogbu iri nri. Atụpụtala na iri ihe mmanye nwere ike ịmalite dị ka ụdị ọgwụgwọ onwe onye iji belata ọnọdụ mmetụta uche na-adịghị mma metụtara ịwepụ na nri ndị na-atọ ụtọ nke ukwuu. Ezubere ọmụmụ a iji chọpụta ma mwepu na-adịghị ala ala, ịnweta nri na-atọ ụtọ nke ukwuu bụ maka mpụta omume ịda mbà n'obi. Maka ebumnuche a, e nyere otu oke ụmụ nwoke Wistar nri nri kwa ụbọchị ụbọchị asaa n'izu (Chow / Chow), ebe e nyere ìgwè nke abụọ nke oke chow maka ụbọchị 5 kwa izu, na-esote ụbọchị 2 iji nweta nri sucrose dị ụtọ nke ukwuu (Chow / Palatable). Na-esochi izu 7 nke mgbanwe nri, a tụlere omume ịda mba n'oge ịwepu na nri dị ụtọ nke ukwuu yana na-eso ụzọ nwetaghachi ya, na-eji ule igwu mmiri amanye, ule oriri sucrose, yana usoro mkpali onwe onye intracranial. Achọpụtara ya Chow / Palatable oke ewepụrụ na nri na-atọ ụtọ nke ukwuu gosipụtara oge enweghị ike ịgagharị na ule igwu mmiri na mbelata oriri sucrose na ule oriri sucrose ma e jiri ya tụnyere njikwa. Chow / Chow oke. N'ụzọ na-akpali mmasị, a kagburu enweghị ike ịgagharị n'ime ule igwu mmiri a manyere site na ime ka ọ dị ọhụrụ nweta nri dị ụtọ nke ukwuu. Enweghị mgbanwe ọ bụla a hụrụ na usoro mkpali onwe onye intracranial. Nsonaazụ ndị a na-akwado echiche ahụ na mwepu na nri dị ụtọ bụ maka mpụta omume ịda mbà n'obi, ha na-egosikwa na iri ihe ike na-ebelata ọnọdụ mmetụta uche na-adịghị mma.

Keywords: anhedonia, ụgwọ ọrụ mkpali ụbụrụ, ịda mbà n'obi, nsogbu iri nri, nri riri ahụ, ule igwu mmiri, oke, sucrose

Okwu Mmalite

Mmụba nnweta ike-oke, nri dị ụtọ nke ukwuu (dịka ọmụmaatụ nri nwere shuga na / ma ọ bụ abụba) bụ ihe na-enye aka na mpụta ụfọdụ ụdị oke ibu na nsogbu iri nri (Yach et al., 2006). A na-eji oke iri nri na-atọ ụtọ nke ukwuu site na nri oke oke, ngwa ngwa na mmanye n'ime obere oge.APA, 2000; Corwin, 2006; Avena et al., 2007; Cottone et al., 2012). N'ihi ụkpụrụ omenala aghọtara maka ịdị gịrịgịrị ma ọ bụ ahụike, usoro iribiga ihe ókè na-esochi ya site na iri nri yana mmachi na nri 'dịkwa mma'. Mgbochi nri, n'aka nke ya, na-akwado agụụ maka nri na-atọ ụtọ karịa ma na-akwalite oke 'nri a machibidoro iwu' na-esote. Ya mere, mgbanwe n'usoro n'etiti nri dị iche iche na-eme ka ọ bụrụ ajọ omume na-adịgide adịgide nke usoro oke / mmachi nke oriri.Polivy na Herman, 1985; Laessle et al., 1989; De Castro, 1995; Mela, 2001).

Usoro oriri ịgba ígwè a ewelitere ajụjụ maka ma 'eriri nri' nwere ike ịdị n'ezie (Corwin na Grigson, 2009; Epstein na Shaham, 2010). Oke ibu na nsogbu iri nri, dị ka ọgwụ riri ahụ, ka akwadoro ka ọ bụrụ ọnọdụ nlọghachi azụ na-adịghị ala ala yana oge ọzọ nke abstinence na nlọghachi site na nri dị ụtọ nke ukwuu na-aga n'ihu n'agbanyeghị nsonaazụ ọjọọ. Edepụtala ọtụtụ ihe atụ n'etiti ịdabere na ọgwụ na-eri nri na oke ibu na nsogbu iri nri, gụnyere enweghị ike ịchịkwa ọgwụ / nri, enweghị ike ịkwụsị ịṅụ ọgwụ ọjọọ / iribiga nri ókè n'agbanyeghị na ịmara ihe ọjọọ, nhụjuanya, na dysphoria mgbe ị na-agbalị izere ya. ọgwụ/nri (Willard, 1991; Geliebter na Aversa, 2003; Steiger et al., 2005; Wolfe et al., 2009).

Ngbanwe site na nti na nkwado na-adịghị mma bụ nke a na-eche na ọ ga-abụ maka mgbanwe site na iji ọgwụ ọjọọ eme ihe gaa na ịdabere na ịṅụ ọgwụ ọjọọ. (Koob na Kreek, 2007; Koob, 2008). N'oge riri ahụ, a na-ekwenye na agụụ na ịṅụ ọgwụ ike na-akwado ya site na ọnọdụ mmetụta uche na-adịghị mma na dysphoria metụtara abstinence (dịka nkwụsị). N'otu aka ahụ, a tụrụ aro na iri nri mmanye nwere ike pụta dị ka ụdị ọgwụgwọ onwe onye iji belata ọnọdụ mmetụta uche na-adịghị mma metụtara ịwepụ na nri ndị na-atọ ụtọ nke ukwuu (Cottone et al., 2009a, 2009b; Parylak et al., 2011). Ịhapụ nri ndị na-atọ ụtọ nke ukwuu nwere ike bụrụ ihe kpatara mmalite nke ọrịa mwepụ nke dysphoria, nchekasị, na anhedonia mara, nke nwere ike, n'aka nke ya, na-ebute nlọghachi na iribiga nri ókè.

N'okwu a, egosila n'oge na-adịbeghị anya na ohere na-adịghị ala ala, nke na-adịte aka na nri ndị na-atọ ụtọ na-arụpụta ọ bụghị naanị na hyperphagia nke nri na-atọ ụtọ nke ukwuu kamakwa n'omume na-adabere na ndọrọ ndọrọ ọchịchị, nke gụnyere hypophagia, ụkọ mkpali iji nweta nri na-adịghị mma, na omume dị ka anxiogenic (Cottone et al., 2008, 2009a, 2009b). Agbanyeghị, a ka amabeghị ma ọnọdụ mmetụta uche na-adịghị mma a hụrụ na mwepụ nke nri na-atọ ụtọ nke ukwuu gụnyekwara omume ịda mbà n'obi ka amabeghị. Ya mere, ọmụmụ ihe a bụ iji chọpụta ma omume ịda mbà n'obi na-eme mgbe mwepu na-adịghị ala ala, ohere na-adịte aka na nri dị ụtọ nke ukwuu. Iji nwalee echiche a, anyị tụlere mpụta nke (i) enweghị ike imeghari, na-eji ule igwu mmiri amanye, (ii) omume dị ka anhedonic, na-atụ oriri nke ngwọta sucrose, na (iii) ụkọ ụgwọ ọrụ ụbụrụ, na-atụ ọnụ ụzọ maka intracranial. mkpali onwe onye (ICSS), na nri oke oke na-agbagharị n'oge mwepu na nri na-atọ ụtọ nke ukwuu yana n'oge enwetaghachi ya.

ụzọ

Ndị isi

Oke Wistar nwoke, na-atụ 180–230 g na ụbọchị 41–47 mgbe ọ bịarutere (Charles River, Wilmington, Massachusetts, USA), nwere ụlọ okpukpu abụọ n'elu waya, oghere plastik (27 × 48 × 20 cm) na awa 12. ntụgharị ọkụ ntụgharị (ọkụ na 9:00 am), na AAALAC-akwado iru mmiri-achịkwa (60%) na okpomọkụ na-achịkwa (22°C) vivarium. Oke nwere ohere ịnweta chow nke ọka (Harlan Teklad LM-485 Diet 7012; 65% kcal carbohydrate, 13% abụba, protein 21%, ike metabolizable 341 cal / 100 g; Harlan, Indianapolis, Indiana, USA) na ịnweta ohere n'efu. mmiri mgbe niile ma ọ bụrụ na akọwapụtaghị ya. Usoro ndị e ji mee ihe n'ọmụmụ ihe a gbadoro ụkwụ na Ụlọ Ọrụ Na-ahụ Maka Ahụ Ike Mba Nduzi maka nlekọta na ojiji nke umu anu ohia (Nọmba mbipụta nke NIH 85-23, emegharịrị 1996) na Cipleskpụrụ nke ilekọta anụmanụ anụmanụ Ụlọ ọrụ nlekọta ahụike na kọmitii ojiji nke Mahadum Boston (IACUC) kwadoro ya.

Nhọrọ nri nwere ike ịnweta n'efu

Emere mgbanwe nri nwere ike ịnweta n'efu dị ka akọwara na mbụ (Cottone et al., 2008, 2009a, 2009b). Na nkenke, ka emechara, e kewara oke oke ụzọ abụọ dabara adaba maka iri nri, ịdị arọ ahụ, na arụmọrụ nri sitere na ụbọchị 3-4 gara aga. Enyere otu otu ohere ịnweta nri chow (Chow) ụbọchị asaa n'izu (Chow / Chow, otu njikwa nke ọmụmụ ihe a) na otu nke abụọ ka e nyere ohere ịnweta chow maka 5 ụbọchị n'izu, na-esote ụbọchị 2 nke ohere n'efu na-eri nri dị ụtọ, chocolate-flavored, nri sucrose dị elu (Palatable; Chow / Palatable). Emere ule omume niile n'ime oke ndị ejirila nri na-eri nri ruo opekata mpe izu asaa. Nri 'chow' bụ ọka a kọwara n'elu nke sitere na Harlan, ebe nri na-atọ ụtọ bụ nri zuru oke, chọkọleti nwere ụtọ, sucrose dị elu (7% kcal), nri dabere na AIN-50A nke yiri ya na macronutrient. nha na ike njupụta na nri chow [ụdị chocolate-flavored Formula 76TUL: 5% kcal carbohydrate, 66.7% abụba, protein 12.7%, ike metabolizable 20.6 kcal / 344 g; TestDiet, Richmond, Indiana, USA; emebere dị ka pellet nri ziri ezi nke 100mg iji bulie mmasị ya (Cooper na Francis, 1979; Ịrụ ọrụ et al., 2001)). Maka nkenke, ụbọchị 5 mbụ (chow naanị) na ụbọchị 2 ikpeazụ (chow ma ọ bụ ụtọ dị ka otu nnwale) nke izu ọ bụla na-ezo aka na nnwale niile dị ka usoro C na P. A naghị enwekwa nri n'otu oge. Mmasị nri ndị ikwu, gbakọọ dị ka pasent nke oriri kwa ụbọchị (kcal) nke nri mbụ n'ihe metụtara nri nke abụọ, bụ ndị a: 5TUL Chocolate Diet (sugary Palatable diet) vs. Harlan LM-485 chow (M± SEM mmasị 90.7 ± 3.6%), dị ka e bipụtara na mbụ (Cottone et al., 2009b). A na-agbakọ arụmọrụ nri dị ka mg arọ ahụ nwetara / kcal ike oriri (Cottone et al., 2009b).

Nnwale igwu mmiri amanye

Emebere ule igwu mmiri a manyere site na ule a kọwara Porsolt et al. (1977) na Castagne et al. (2011), iji nnukwu dayameta cylinder na mmiri miri emi na-amụba uche, dị ka akọwara na mbụ (Wieland na Lukki, 1990; Detke et al., 1995; Sabino et al., 2009a). N'okpuru ọkụ, oke (n= 19) etinyere n'otu n'otu na cylinders polypropylene abụọ doro anya (38 cm dị elu, dayameta 27 cm) nke kewara site na ihuenyo opaque. Silinda ndị ahụ nwere 23-25 Celsius C, 24 cm miri emi. N'ime omimi a, oke enweghị ike ịkwado onwe ha site na iguzo ọtọ (Wieland na Lukki, 1990; Detke et al., 1995). A gbanwere mmiri n'etiti isiokwu. Emere oge igwu mmiri abụọ: ihe nleba anya nke nkeji iri na ise nke mbụ, elekere 15 gachara site na nnwale 24 nkeji. Na-esochi oge igwu mmiri ọ bụla, a na-ewepụ oke ndị ahụ na cylinders, akpọnwụọ, tinye ya n'ime ụlọ ọkụ maka nkeji iri, wee laghachi n'ụlọ ha. Edere ihe onyonyo onyonyo ma mechaa jiri oge were were akara akara oge ule; A na-ekpebi oge eji eme njem, igwu mmiri na ịrị elu. Chow / Palatable A na-eri oke oke nri maka izu asaa dịka akọwara n'elu. N'ime izu nke asatọ nke ịgba ígwè, Chow / Palatable a nwalere oke n'oge nke C ma ọ bụ P, yana Chow / Chow A na-anwale oke oke n'ụdị ihe dị n'etiti. Emere ihe nleba anya nke 15-min 1 ụbọchị mgbe mgbanwe ahụ gasịrị (P → C ma ọ bụ C → P), ebe a na-eme nnwale 5-min ka awa 24 gachara. Chow / Chow A nwalere oke njikwa n'otu oge n'ụdị ihe dị n'etiti. Nri dị iche iche dị n'efu ruo oge nyocha. Oke dị ihe dịka ọnwa 4 n'oge ule igwu mmiri amanye.

Nnwale oriri nke Sucrose

Emebere ule oriri sucrose site na Chen et al. (2012). Oke sitere na ọmụmụ ICSS (n= 15, ewepụrụ isiokwu na ọmụmụ ihe n'ihi mmasị ebe) ekpughere na 0.8% sucrose solution na nri, mmiri na ngwọta dị ụtọ dị na ụlọ ha ma ọ dịkarịa ala 1 izu iji mara ha ihe ọṅụṅụ na-atọ ụtọ. . Mkpughe gara aga mere n'oge mgbanwe nri ma jiri ya mee ihe iji zere ịzere ihe ụtọ ọhụrụ ahụ n'ihi neophobia (D'Souza na Markou, 2010). A na-agbanwe ọnọdụ nke sucrose na karama mmiri kwa ụbọchị iji gbochie mmasị ebe. N'ụbọchị mbụ nke usoro P na C, a na-ahapụ oke ka ọ ṅụọ 0.8% sucrose ngwọta nke enyere n'ụlọ ha maka 1 h n'oge ọgba aghara. A tụlere oriri sucrose n'ụdị C na P n'otu anụmanụ site na iji imewe ihe dị n'ime. A tụrụ oriri sucrose dị ka ml/kg nke arọ ahụ.

Intracranial mkpali onwe

Ịwa ahụ maka ntinye electrode

Mgbe emechara, oke (n= 16) etinyere n'otu akụkụ nke 0.125mm dayameta bipolar igwe anaghị agba nchara (MS303/3-B/SPC, ogologo 10.5mm; Plastics One, Roanoke, Virginia, USA) n'ime aka ekpe ma ọ bụ n'akụkụ aka nri etiti ụbụrụ ụbụrụ n'ogo. nke hypothalamus mpụta site na iji nhazi ndị a: AP - 0.5mm site na bregma, ML ± 1.7mm, DV - 9.7mm site na okpokoro isi ya na ogwe incisor setịpụrụ 5.0mm n'elu ahịrị interaural, dị ka atlas nke Pellegrino (1979). Ejidere skru igwe anaghị agba anọ n'okpokoro oke oke gburugburu elektrọd. A na-etinye resin na-emezigharị eze (Henry Schein Inc., Melville, New York, USA) na simenti acrylic na-eme pedestal nke kwadoro electrode ahụ. Ịwa ahụ gụnyere ịgbanye oke (isoflurane, 2-3% na oxygen) ma chekwaa ha na Kopf Instruments stereotaxic frame (David Kopf Instruments, Tujunga, California, USA; Cottone et al., 2007). E kwere ka ndị mmadụ nwetaghachi site na ịwa ahụ ma ọ dịkarịa ala ụbọchị 7 tupu mmalite nke ọzụzụ ICSS.

ngwa

Ọzụzụ ICSS na ule mere n'ime ụlọ nyocha polycarbonate / aluminom modular operant doro anya nke etinyere n'otu akụkụ na-ebelata ụda na ikuku ikuku (66 × 56 × 36 cm) (Med Associates, St Albans, Vermont, USA)Blasio et al., 2011; Sabino et al., 2011). Ụlọ nke ọ bụla nwere ala grid ma enwere ihe ndọghachi azụ na mgbidi dị n'akụkụ (Sabino et al., 2006, 2009b). Ejikọtara ihe ndị ahụ na sekit mkpali ọkụ eletrik site na ụzọ bipolar (Plastics One) na kọntaktị swivel commutators (Plastics One). A na-eji ihe na-akpali akpali square ebili mmiri na-adị ugbu a (Med Associates) iji wepụta mkpali ụbụrụ eletrik. Kọmputa nwere mkpebi 10-ms na-achịkwa ọrụ mmemme niile.

Intracranial usoro mkpali onwe

Mgbe agbakechara site na ịwa ahụ, a na-ekpebi ọnụ ụzọ maka mkpali ụbụrụ na-akwụghachi ụgwọ site na iji usoro ike siri ike ugbu a na-adabereghị na ọnụọgụ nke Kornetsky na ndị ọrụ ibe ha mere.Marcus na Kornetsky, 1974; Esposito na Kornetsky, 1977; Kornetsky et al., 1979) ma kọwaa n'ụzọ zuru ezu site na Markou na Koob (1991, 1992). A zụrụ oke ka ọ na-atụgharị n'usoro nkwado 1 n'usoro n'usoro (FR) iji nweta ụgbọ oloko 500-ms nke mkpali eletriki. Ihe mkpali ọ bụla nwere ụgbọ oloko 500-ms nwere obosara usu nke 0.2 ms yana igbu oge 0.2 ms n'etiti ihe dị mma na nke na-adịghị mma. A nwalere oke niile na ugboro ugboro 50 Hz, ma ọ bụrụ na ọkwa dị ugbu a nke ha zara dị n'okpuru 80 ma ọ bụ karịa 120 μA na enweghị ntụkwasị obi, mgbe ahụ, a na-ahazi ugboro ole ahụ n'otu n'otu maka anụmanụ ọ bụla iji ruo ogo achọrọ nke ugbu a ma na-edobe ya mgbe niile. maka usoro nyocha niile (Kenny na Markou, 2005). Ozugbo arụrụ ọrụ FR1 kwụsiri ike na-aza maka mkpali eletriki, a tụlere ọnụ ụzọ ICSS site na iji usoro a. Na mmalite nke ule ọ bụla, oke na-enweta ihe mkpali na-adịghị agbanwe agbanwe (S1), mgbe nke ahụ gasịrị, ha nwere ohere, n'ime obere oge 7.5 s, iji lever press, nke rụpụtara na nnyefe nke mkpali na-adịgide adịgide (S2) bụ nke yiri ya. S1 gara aga. Oge nke 7.5–22.5 s (nkezi 15 s) gafere n'etiti nnyefe S2 na nnyefe nke S1 na-esote. Ọ bụrụ na ọ nweghị nzaghachi mere, oge a malitere na njedebe nke oge 7.5-s ekenyela maka nzaghachi. Emebere oge ndị a ka ụmụ anụmanụ ghara 'ịkọ amụma' nnyefe S1 na-esote. A'trial' nwere ihe ngosi ise nke S1 n'ogo siri ike ugbu a (na μA). Akara nzaghachi atọ ma ọ bụ karịa na ike ahụ dị ka gbakwunyere (+) maka nnwale ahụ, ebe nzaghachi abụọ ma ọ bụ ole na ole ka agbatara dị ka mwepu (-) maka nnwale ahụ. Ọ bụrụ na anụmanụ ahụ nwetara akara (+) maka nnwale nke mbụ, nnwale nke abụọ malitere na ike nke 5 μA dị ala karịa nke mbụ. Ike dị ugbu a gara n'ihu na-ebelata site n'otu ike ahụ ruo mgbe anụmanụ ahụ nwetara akara (-) maka ule abụọ na-esochi. Mgbe nke a mere, ike dị ugbu a na nnwale nke abụọ nke enwetara akara (-) ugboro ugboro ma ihe ndị dị ugbu a na-agbago site na 5 μA maka ule ọ bụla ruo mgbe anụmanụ ahụ nwetara (+) maka ule abụọ na-esochi. A kọwapụtara otu ọ bụla nke nrịgo ma ọ bụ na-agbada ugbu a dị ka 'kọlụm', na ngụkọta nke kọlụm isii na-agbadata/nrịgo ka emere maka nnọkọ ọ bụla. A kọwapụtara ike dị n'etiti (+) na (-) dị ka ọnụ ụzọ kọlụm. A gbakọrọ ọnụ ụzọ maka nnọkọ nke ọ bụla dị ka ihe nrịbama nke ọnụ ụzọ kọlụm anọ ikpeazụ; ya mere, ewepụrụ ọnụ ụzọ kọlụm nke mbụ na nke abụọ. Mmụba nke ọnụ ụzọ ụgwọ ọrụ gosiri na a naghị aghọtacha mkpali mkpali ndị a na-aghọtabu dị ka ihe na-enye ume, na-egosipụta mbelata ọrụ ụgwọ ọrụ ma na-atụ aro ọnọdụ ịda mbà n'obi. N'aka nke ọzọ, iwetu ọnụ ụzọ ụgwọ ọrụ gosipụtara mmụba ụgwọ ọrụ (Markou na Koob, 1991).

Iji kụda isiokwu a ịzaghachi n'oge etiti oge ikpe, nzaghachi ọ bụla n'ime oge a yigharịrị mmalite nke S1 maka 22.5 s ọzọ (ogologo oge gafere ma ọ bụ hà nhata na oge mbụ enweghị usoro nke etiti oge ikpe. ). Edekọrọ nzaghachi 'ataramahụhụ' ndị a dị ka nzaghachi oge agwụla ma na-anọchi anya nha nke mkpali-dị ka mgbochi nke ịzaghachi. Nzaghachi lever karịrị akarị n'ime 2 s ka nzaghachi mbụ ahụ nweteghị nsonaazụ ma dekọọ ya dị ka nzaghachi ụyọkọ.

Akọwapụtara nkwụsị nzaghachi dịka oge n'etiti nnyefe nke S1 na nzaghachi anụmanụ na lever. A kọwapụtara nkezi nzaghachi nzaghachi maka oge ule ọ bụla dị ka nkwụsị nzaghachi nzaghachi nke ule niile nke anụmanụ zara. Mgbe agbakechara site na ịwa ahụ, a zụrụ oke kwa ụbọchị na usoro ICSS 2 h mgbe mgbanwe nri gasịrị. Na-eso nkwụsi ike ọnụ ụzọ, oke nwere ịgba ígwè nri. Nyere ogologo nke mgbanwe nri (izu 7), a na-anwale anụmanụ naanị otu ugboro n'izu iji zere mfu nke etinyere electrode. E nyere oke ohere ka a na-azụghachi ya kwa ụbọchị n'ime izu nke asaa nke ịgba ígwè nri, na n'ikpeazụ a nwalere ha kwa ụbọchị n'ime izu 7, 8, na 9 nke usoro ịgba ígwè nri.

Nyocha data

Achọpụtara enweghị ike ịgagharị, igwu mmiri, na oge ịrịgo na ule igwu mmiri amanye n'oge mbụ na ụbọchị nke abụọ nke ule ahụ site na iji nyocha otu ụzọ nke ọdịiche (ANOVAs), na ọnọdụ nri dị ka ihe dị n'etiti ihe. ANOVA ụzọ abụọ nwere ọnọdụ nri dị ka ihe dị n'etiti ihe na-akpata na oge dị ka ihe dị n'ime ka ejiri nyochaa oge nke enweghị ike imeghari. A na-enyocha oriri nke Sucrose site na iji ụzọ abụọ ANOVA nwere usoro nri dị ka ihe dị n'etiti isi na usoro dị ka ihe dị n'ime. Ahaziziri Bonferroni t- eji ule tụnyere Cka/Chow na Chow / Palatable otu dị iche iche n'oge usoro abụọ ahụ, na ọkwa nke mkpa e debere na P ọnụ ahịa na-erughị 0.025. Ọnụ ụzọ ICSS kwa ụbọchị na latencies ịzaghachi bụ nkezi n'ime usoro nke ọ bụla n'ime izu 8, 9, na 10. A na-enyocha ha site na iji ụzọ atọ agwakọta ANOVA nwere usoro nri dị ka ihe dị n'etiti isi na izu na oge dịka ihe dị n'ime. Akụrụngwa/ngwugwu ihe osise ejiri mee ihe bụ Systat 11.0, SigmaPlot 11.0 (Systat Software Inc., Chicago, Illinois, USA), InStat 3.0 (GraphPad, San Diego, California, USA), Statistica 7.0 (Statsoft Inc., Tulsa, Oklahoma, USA). ), PASW Statistics 18.0 (SPSS Inc., Chicago, Illinois, USA), na G*Power 3.1 (http://www.psycho.uni-duesseldorf.de/aap/projects/gpower/).

Results

Mmetụta mgbanwe nri na-atọ ụtọ na oge enweghị ike ime na ule igwu mmiri amanye

Dị ka egosiri na 1a fig, Chow/Palatable oke ewepụrụ site na nri na-adịghị ala ala, ohere na-adịte aka na nri na-atọ ụtọ gosipụtara oge adịghị ike na-abawanye na nkeji iri na ise [15].F(2,16) = 4.37, P<0.05] na ule nkeji 5 [F(2,16) = 3.78, P<0.05], ma e jiri ya tụnyere Chow / Chow oke. Mmụba nke oge enweghị ike nke oke oke na-ewepụ nri dị ụtọ bụ ~ 97% na nnọkọ pretest yana ~ 187% na nnọkọ ule, ma e jiri ya tụnyere oke njikwa. N'ụzọ na-akpali mmasị, na-apụghị imeghari oge nke Chow / Palatable oke, mgbe a nwalere mgbe enyere nri dị ụtọ (P phase), adịghị iche na nke njikwa Chow / Chow oke n'ime nkeji iri na ise ma ọ bụ nwale nkeji ise. Ebe ọ bụ na enweghị ike ịmegharị ule igwu mmiri na-amanye n'otu anụmanụ ahụ, a na-eji ihe eji eme ihe n'etiti ihe. Otú ọ dị, n'ihi na nke obere sample size nke Chow / Chow isiokwu dị maka ọmụmụ ihe a (n= 19, nha mmetụta = 0.4, α njehie puru omume = 0.05, ike = 0.4), na Chow / Chow A na-ejikọta anụmanụ ndị a nwalere n'akụkụ abụọ ahụ n'otu ìgwè, n'ihi na ha adịghị iche na ọnụ ọgụgụ. Maka izu oke, amanye amanye igwu mmiri na-anwale data immobility, tụgharịrị n'ime usoro C na P maka otu niile, bụ ndị a (pụtara ± SEM): pretest C phase 107.8± 16.4 vs. 323.3 ± 33.3, pretest P phase 201.1 ± 33.5 vs. 180.4 ± 61.5; nwalee C nkeji 23.8± 14.7 vs. 101.2±19.1, nwale P agba 42.9±4.8 vs. 61.0±17.1, Chow / Chow na Chow / Palatable, n'otu n'otu. Ọzọkwa, ụzọ abụọ ANOVA mere n'oge bins nke enweghị ike ịgafe na 15min nke pretest ma ọ bụ 5 min nke ule ahụ gosipụtara mmetụta dị mkpa nke Usoro Nri nri [pretest: F(2,16) = 4.37, P<0.05; nwale: F(2,16) = 3.78, P<0.05] na nke oge [pretest: F(4,64) = 18.55, P<0.001; nwale: F(4,64) = 15.44, P<0.001], mana mmekọrịta oge × Nri nri abụghị ihe dị mkpa. F(8,64)=1.06, NS; nwale: F(8,64)=0.97, NS].

Mmetụta na-adịghị ala ala, ohere na-adịte aka na nri dị ụtọ nke ukwuu na enweghị ike imegharị, enyocha ya site na iji ule igwu mmiri na oke Wistar (pụtara ± SEM: n =19), na pretest 15-min (panel aka ekpe), na ule 5-min (panel aka nri). *Chow / Palatable (C nkeji) ...

A hụkwara mmetụta dị ịrịba ama na oge igwu mmiri na ma pretest [F(2,16) = 4.50, P<0.05] na oge ule [F(2,16) = 5.27, P<0.02], ya na nri na-atọ ụtọ ewepụrụ Chow / Palatable oke igwu mmiri ~ 22 na ~ 27% erughị Chow / Chow oke n'oge nnọkọ abụọ ahụ, n'otu n'otu (data egosighi). Ọzọ, oge igwu mmiri nke Chow / Palatable oke, nke a nwalere n'oge oge P, adịghị iche na njikwa Chow / Chow oke na nnọkọ ọ bụla. Oge ịrị elu adịghị iche n'etiti otu n'ime ma ọ bụ pretest [F(2,16) = 0.52, NS] ma ọ bụ oge ule [F(2,16)=3.13, NS] (data egosighi). Ọ dịghị ihe dị iche na arọ ahụ n'etiti otu dị iche iche n'oge ule [pụtara ± SEM: 558 ± 26.8 vs. 519 ± 21.8 vs. 533 ± 11.4; F(2,16)=0.92, NS, Chow / Chow vs. Chow / Palatable n'usoro P- vs. Chow / Palatable na ngalaba C, n'otu n'otu].

Mmetụta nke mgbanwe nri na-atọ ụtọ na ule oriri sucrose

Dị ka egosiri na Fig. 2, oke ewepụrụ site na-adịghị ala ala, ohere na-adịte aka na nri dị ụtọ nke ukwuu gosipụtara mbelata oriri sucrose ma e jiri ya tụnyere ya. Chow / Chow Oke ndị a na-azụkarị ọkọlọtọ chow [Nri Nri: F(1,13) = 6.74, P<0.05; Usoro: F(1,13) = 26.681, P<0.001; Usoro nri × Usoro: F(1,13)= 0.084, NS. N'ezie, Bonferroni gbaziri t-Nnwale gosiri na n'ime ụbọchị mbụ nke ndọrọ ego si na chocolate-flavored nri (C nkeji), Chow / Palatable oke riri sucrose nke ukwuu ma e jiri ya tụnyere Chow / Chow oke. Ihe oriri sucrose nke Chow / Palatable oke ndị ewepụrụ na nri dị ụtọ nke ukwuu belatara ihe karịrị 50% ma e jiri ya tụnyere Chow / Chow oke. Enwere mbelata nke oriri sucrose n'oge usoro P; otu o sila dị, omume a adịchaghị mkpa na mkpokọta. Enweghị ọdịiche dị ịrịba ama na ịdị arọ ahụ zuru oke n'etiti otu dị iche iche n'oge ule (pụtara ± SEM: 575 ± 28.4 vs. 591 ± 29.5; t(15)=0.69, NS, Chow / Chow vs. Chow / Palatable, n'otu n'otu).

Fig. 2

Mmetụta nke na-adịghị ala ala, ohere na-adịte aka na nri dị ụtọ nke ukwuu na oriri sucrose na oke Wistar (pụtara ± SEM: n= 15). *Chow / Palatable dị iche na Chow / Chow, P<0.05 (Bonferroni deziri t-nnwale).

Mmetụta nke mgbanwe nri na-atọ ụtọ na ọnụ ụzọ mkpali onwe onye intracranial.

Ọnụ ego nke ICSS Chow / Chow na Chow / Palatable A tụlere otu dị iche iche n'oge oge mwepụta (C) na usoro ntinye ọhụrụ (P) maka izu atọ na-esochi (8, 9, na 10). Dị ka ụzọ atọ ANOVA gosipụtara ma gosi na Fig. 3, ohere na-adịte aka na nri dị ụtọ nke ukwuu enweghị mmetụta dị ukwuu na ọnụ ụzọ ICSS [Nri Nhazi: F(1,14)=0.05, NS; Usoro nri × Usoro: F(1,14)=1.58, NS; Usoro nri × izu: F(2,28)=0.29, NS; Usoro ihe oriri × Agba × izu: F(2,28)=0.24, NS]. N'otu oge ahụ, mgbanwe nri na-atọ ụtọ nke ukwuu emetụtaghị latency ịzaghachi [Nhazi Nri: F(1,14)=0.54, NS; Usoro nri × Usoro: F(1,14)=2.39, NS; Usoro nri × izu: F(2,28)=2.61, NS; Usoro ihe oriri × Agba × izu: F(2,28)=0.30, NS] (Isiokwu 1). Enweghị ọdịiche dị ịrịba ama na ịdị arọ ahụ zuru oke n'etiti otu dị iche iche n'oge ule [pụtara ± SEM: 527.89 ± 15.15 vs. 507.0 ± 19.74; t(14)=0.40, NS, Chow / Chow vs. Chow / Palatable, otu ọ bụla].

Fig. 3

Mmetụta nke na-adịghị ala ala, ohere na-adịte aka na nri dị ụtọ nke ukwuu na ụgwọ ọrụ ụbụrụ nke a na-enyocha na-atụle ọnụ ụzọ mkpali onwe onye intracranial (mgbanwe pasent site na njikwa. Chow / Chow) na oke Wistar (pụtara ± SEM: n= 16).

Mmetụta nke na-adịghị ala ala, ohere na-adịte aka na nri dị ụtọ nke ukwuu na latencies iji zaghachi enyocha site na iji usoro mkpali onwe onye na oke Wistar (pụtara ± SEM: n= 16)

Nkwurịta

Nsonaazụ nke ọmụmụ a na-egosi na mwepu site na nri na-adịghị ala ala, ohere na-adịte aka na nri na-atọ ụtọ bụ maka mpụta nke enweghị ike imegharị na ule igwu mmiri amanye. Ọzọkwa, cycled Chow / Palatable oke gosipụtara omume anhedonic dị ka egosipụtara site na mbelata oriri nke ngwọta sucrose 0.8% maara nke ọma. N'ụzọ na-akpali mmasị, nkwụsịtụ, ịgbatị ohere ịnweta nri na-atọ ụtọ emeghị ka ụgwọ ọrụ dị na paradaịs ICSS, nke a ga-atụgharị dị ka ụgwọ ọrụ ụgwọ ọrụ ụbụrụ.

Mgbe e wepụrụ nri na-atọ ụtọ nke ukwuu, oke na-agba ịnyịnya na-egosi mmụba nke enweghị ike imegharị na ule igwu mmiri amanye. N'otu aka ahụ dị mkpa, oge na-adịghị agbanwe agbanwe Chow / Palatable oke laghachiri n'ọkwa njikwa ka ọ nweteghachiri na nri nwere shuga. Uru ọgwụgwọ paradoxical nke nri na-atọ ụtọ nke ukwuu hụrụ na ule igwu mmiri amanye kwekọrọ na nsonaazụ nchebe nke nri nwere oke abụba megide ụdị mmụọ ịda mbà n'obi dị ka omume phenotype kpatara nrụgide mmalite ndụ ma ọ bụ nrụgide na-adịghị ala ala (Maniam na Morris, 2010a, 2010b, 2010c; mkpịsị aka et al., 2011). N'ezie, egosiri nri nwere nnukwu abụba na-atọ ụtọ ka ọ na-emeziwanye enweghị ike ime nke ọma nke nkewa nne na enweghị njikwa na-ebute (Maniam na Morris, 2010a, 2010b, 2010c). Ọzọkwa, a na-echebe ụmụ oke na-eri nri nwere nnukwu abụba pụọ na mmetụta ịda mbà n'obi na-akpata site na nrụgide psychosocial na-adịghị ala ala na-enweghị atụ.mkpịsị aka et al., 2011). Nkọwa ọzọ nke na-abawanye oge enweghị ike imeghari Chow / Palatable oke nwere ike ịbụ n'ihi na mma sere n'elu ike n'ihi na nke na-amụba aru arọ nwere ike chịrị ka ndị abụọ dị iche iche adịghị iche nke ukwuu na ahu arọ (Cottone et al., 2008, 2009a). A ga-achọrọ ọmụmụ ndị ọzọ iji chọpụta izu ole nke ịgba ígwè chọrọ iji zụlite omume ịda mbà n'obi na / ma ọ bụ nchekasị na-esote nkwụsịtụ site na ịnweta nri dị ụtọ nke ukwuu, yana ogologo oge àgwà ọjọọ ahụ na-aga n'ihu na-esote mgbanwe na Nri nri chow na-amasịkarị.

Amara ule igwu mmiri a manyere na ọ nwere ezigbo amụma amụma dịka ọ na-achọpụta ọgwụ antidepressants na-eji ụlọ ọgwụ eme ihe nke ọma (Borsini na Meli, 1988). Agbanyeghị, ịkọwa enweghị ike ịgagharị na ule igwu mmiri amanye dị ka ihe metụtara ịda mbà n'obi ka na-esekarị okwu. N'ime afọ ndị gafeworonụ, enweela ọtụtụ nkọwa na echiche gbasara ihe nzaghachi enweghị ike pụtara na ule igwu mmiri amanye. A na-akọwa enweghị ike ịgagharị na ule igwu mmiri mmanye dị ka omume na-agafe agafe na mmekọrịta omume nke ọnọdụ ọjọọ (Cryan na Mombereau, 2004; Slattery na Cryan, 2012). Atụwala enweghị ike ịgagharị na ule igwu mmiri amanye dị ka enweghị ike ma ọ bụ enweghị mmasị ịnọgide na-agba mbọ, kama ịbụ hypoactivity n'ozuzu ya (Willner, 1990); Ọjụjụ a na-ejikọta ya na nchọpụta ụlọ ọgwụ na ndị ọrịa dara mbà n'obi na-egosi adịghị ike nke psychomotor na ule ndị chọrọ mgbalị na-adịgide adịgide, ya mere na-enye ụfọdụ nkwado maka ule a.Weingartner na Silberman, 1982). Ọ bụ ezie na ekwesịrị ịkpachara anya ka ịzenarị oke nke ịgụ ihe omume na ule igwu mmiri amanye, ọ dịkwa mma ịmara na enweghị ike imeghari na ule igwu mmiri a manyere na-ebute site na ọtụtụ ihe gụnyere mkpụrụ ndụ ihe nketa.West na Weiss, 1998), mmetụta nke nrụgide (Solberg et al., 1999; Alonso et al., 2000; Tannenbaum et al., 2002), mgbanwe na oriri oriri (Alcaro et al., 2002), na mwepu ọgwụ ike (Criyan et al., 2003). Ọtụtụ n'ime ihe ndị a na-emetụtakwa ma ọ bụ gbanwee site n'ụzọ nke nnukwu ịda mbà n'obi n'ime mmadụ. Ya mere, ule igwu mmiri na-amanye yiri ka ọ na-atụle akụkụ omume nke dị mkpa na ịda mbà n'obi ma gosipụta onwe ya dị ka ihe nlereanya mara mma maka ịlele ihe ndị metụtara ịda mbà n'obi na anụmanụ.

Anyị gosipụtara na oke ndị nwere ohere na-agafeghị oke na nri dị ụtọ na-egosi mbelata oriri nke sucrose. Sucrose bụ ihe na-akwado eke; Ya mere, a na-atụpụta mbelata oriri ma ọ bụ mmasị maka ngwọta sucrose iji gosipụta mbelata mmetụta maka ụgwọ ọrụ yana, n'ozuzu, anhedonia (Papp et al., 1991; Muscat na Willner, 1992; D'Souza na Markou, 2010). Isi okwu mkparịta ụka dị mkpa metụtara mmetụta na-emegiderịta onwe ya na oriri sucrose hụrụ mgbe ewepụrụ oke na nri shuga na-atọ ụtọ. Otu nwere ike ịtụ anya na oke ndị na-ezere nri shuga ga-abawanye, kama ibelata, oriri nke sucrose ngwọta n'ihi mmetụta enweghị ike sucrose. Otú ọ dị, ngwọta a na-eji nyochaa anhedonia na ọmụmụ ihe a nwere pasent dị ala nke sucrose (0.8%), dịka ọ na-ahụkarị maka ụdị ọmụmụ ihe a.Rygula et al., 2005; D'Souza na Markou, 2010; Chen et al., 2012), mana n'ụzọ doro anya megidere nri dị ụtọ nke ukwuu, nke nwere pasentị sucrose dị elu (~ 50%). Ya mere, ihe ụtọ abụọ ahụ doro anya na ha enweghị ụgwọ ọrụ.

Ihe oriri sucrose nke Chow / Chow na Chow / Palatable Otu dị iche iche na-adịgasị iche dị ka ọrụ nke usoro ahụ, dịka usoro siri ike gosipụtara (P= 0.08) nke mmekọrịta dị n'etiti Usoro Nri na Usoro ihe. Ntụle post-hoc gosiri na ndị otu dị iche iche naanị na usoro C, mana ọ bụghị n'usoro P, na-atụ aro na ịbanyeghachi na nri dị ụtọ nke ukwuu nwere ike ime ka omume ahụ dị ka anhedonic dị ka nke a hụrụ na ule igwu mmiri amanye. . Nsonaazụ ndị a kwekọrọ na ikike akọpụtara nke nri nkasi obi, dị ka nri nwere oke abụba, iji tụgharịa anhedonia nke nkewa nke nne na-akpata, tụrụ dị ka mbelata mmasị maka ngwọta sucrose. Agbanyeghị, ọ dị mkpa iburu n'uche na, ebe ọ bụ naanị na enwere mmekọrịta na-enweghị isi n'etiti ihe abụọ a, enwere ike ịrụ ụka na mbelata oriri nke 0.8% sucrose n'ozuzu ya. Chow / Palatable Otu nwere ike ịdabere na mmegharị mmetụta uche, ebe obibi hedonic, ma ọ bụ ọdịiche hedonic na-adịghị mma n'ihi mkpughe na-adịghị ala ala na nri sucrose 50%.

Nsonaazụ nke ọmụmụ a na-akwado echiche ahụ na ohere na-adịghị ala ala na-enweta nri ndị na-atọ ụtọ nke ukwuu bụ maka mpụta mmetụta mmetụta uche na-adịghị mma yana na ịnwetaghachi ya na-enwe ike ibelata mmetụta na-adịghị mma na-ewepụ ya.Cottone et al., 2008, 2009a, 2009b; Parylak et al., 2011), dị ka ihe a na-eche maka mmepe nke ịdabere na ọgwụ ọjọọ (Koob na Kreek, 2007; Koob, 2008). Ewepụla ọgwụ ọjọọ egosila na ọ na-esonyere ya na omume ịda mbà n'obi dịka mmụba omume na ule igwu mmiri, mbelata oriri sucrose, ma ọ bụ mbelata ọrụ ụgwọ ọrụ ụbụrụ na ICSS. N'ezie, ụbara enweghị ike ịgagharị na ule igwu mmiri a manyere ka egosiri n'oge ịwepụrụ nicotine (Picciotto et al., 2002; Mannucci et al., 2006; Renoir et al., 2012ethanol (Getachew et al., 2010; Walker et al., 2010; Williams et al., 2012), cocaine (Overstreet et al., 2000; Filip et al., 2006; Igha et al., 2008), amphetamine (Criyan et al., 2003MDMA (McGregor et al., 2003; Renoir et al., 2008), opiates (Anraku et al., 2001; Chartoff et al., 2012na phencyclidine (PCP)Noda et al., 1995). Ọzọkwa, nnukwu ihe akaebe dị na-egosi na ọgwụgwọ na-adịghị ala ala na ọgwụ ọjọọ gụnyere amphetamine (Barr na Phillips, 1999; Der-Avakian na Markou, 2010), nicotine (Ribeiro-Carvalho et al., 2011na cannabinoids (Rubino et al., 2008; Bambico et al., 2010) nwere ike imepụta anhedonia n'oge mwepụ, dịka atụpụtara site na mbelata oriri sucrose / saccharin. Na mgbakwunye, mwepu na ọgwụ ọjọọ eme ihe na-ebute mmụba n'atụghị egwu na ọnụ ụzọ ụgwọ ọrụ maka ICSS, mmetụta nke amphetamine na-ekekọrịta (Paterson et al., 2000), cocaine (Markou na Koob, 1991), mmanya (Schulteis et al., 1995), THC (Ugba na Vorel, 1998), na nicotine (Igha-Jọdan et al., 1998). A hụkwara ọkwa dị elu na ọnụ ụzọ ICSS mgbe mwepu na-ebute ọgwụ na opiate na nicotine.Schulteis et al,, 1994; Igha-Jọdan et al., 1998; Kenny na Markou, 2006). Mwepụ a na-ebughị ibu bụ usoro nke a na-eji onye na-emegide ya gbochie ọrụ na-aga n'ihu nke ọgwụ na-agba ume na ebumnuche nnabata. Usoro a na-eweta oge nwepụ n'okpuru njikwa nnwale na ọ bụ ngwá ọrụ dị irè maka ịmụ usoro ịdabere na ya mgbe ọ na-esiri ike ịlele ma ọ bụ nweta n'onwe ya.

N'ụzọ dị ịtụnanya, n'ime ọmụmụ ihe a, ohere ị nweta nri na-atọ ụtọ nke ukwuu emetụtaghị ọnụ ụzọ ICSS. A mụọbeghị mmetụta nke ịnweta ụtọ ụtọ ma ọ bụ ihe ụtọ na-arụ ọrụ ụgwọ ọrụ ụbụrụ nke ọma, na nchoputa ndị dị ugbu a dị iche. Sukhotina et al. (2003) gosipụtara na enweghị ike sitere na onye na-akwado ndị na-abụghị ọgwụ, saccharin - ihe ụtọ na-abụghị calorie - adịghị ejikọta ya na omume ịda mbà n'obi ma nwee ike belata ọnụ ụzọ ICSS. Na ntule ndịiche, Johnson na Kenny (2010) gosiri n'oge na-adịbeghị anya na 18-23 h / ụbọchị ịnweta nri cafeteria, nke na-ebute mmepe nke oke ibu, nwere ike ịbawanye ọnụ ahịa ụgwọ ọrụ. Ya mere, enweghi mmetụta na ọnụ ụzọ ICSS na ọmụmụ ihe anyị nwere ike ịkọwa site n'ọtụtụ ihe dị iche iche, gụnyere ihe ụtọ eji eme ihe, ogologo oge ịnweta nri, na mmepe - ma ọ bụ - oke ibu. Na mgbakwunye, nkọwa ọzọ maka enweghị mgbanwe ọ bụla na mberede na ọnụ ụzọ ICSS na Chow / Palatable oke bụ na mwepu nwere ike ịdị mkpa ka ọ gbasa ngwa ngwa n'usoro ọgwụ iji chọpụta mperi na ọrụ ụgwọ ọrụ ụbụrụ. Ọzọkwa, ọ ga-ekwe omume na oke ndị na-eri nri na-egosi mgbanwe na ụgwọ ọrụ ụbụrụ n'oge ụbọchị dị iche na nke a họọrọ na ọmụmụ ihe ugbu a. Ya mere, ọnọdụ ọzụzụ a kapịrị ọnụ nwekwara ike ịpụta maka enweghị mmetụta na paradaịs ICSS. A ga-achọrọ ọmụmụ ihe n'ọdịnihu iji kwado echiche ndị a. Ọdịiche dị n'etiti nsonaazụ ọjọọ enwetara na nnwale ICSS na nsonaazụ dị mma a hụrụ na oriri sucrose na nnwale igwu mmiri bụ ihe na-atọ ụtọ mkparịta ụka. Ọ bụ ezie na ule ndị e ji mee ihe n'ọmụmụ ihe a, ha nile na-enyocha àgwà ịda mbà n'obi, ha na-atụle ihe omume omume dị iche iche nke ọma: ule igwu mmiri na-amanye na-egosi enweghị ike imegharị na ọnọdụ na-eyi ndụ egwu; Nnwale oriri sucrose na-atụle mkpali isiokwu maka mkpali na-akwụghachi ụgwọ; na ICSS, site na mkpali kpọmkwem nke neurons nke ngwugwu etiti etiti dị n'ihu, na-atụle ike kacha nta nke ugbu a na-ewusi omume ike. N'iburu n'uche ụdị dị iche iche nke paradigms ejiri mee ihe, ọ ga-abụ na ule atọ ahụ na-adabere na mkpụrụ ndụ neurobiological dị iche iche nakwa na ndị na-eme ihe dị iche iche na-etinye aka. Ya mere, ịdị n'otu nke nsonaazụ na ule dị iche iche nwere ike ọ gaghị abụ naanị nsonaazụ a tụrụ anya ya. Dịka ọmụmaatụ, na ọmụmụ ihe ọzọ, nke yiri ihe a hụrụ ebe a, nrụgide dị nro na-adịghị ala ala nwere ike ibelata oriri nke ngwọta sucrose, mana ọ gbanweeghị arụmọrụ ICSS na oke mkpuchi PVG.Nielsen et al., 2000).

Nsonaazụ nke ọmụmụ a na-akwado nkwupụta ahụ bụ na oge adịghị ala ala, ịnweta nri na-atọ ụtọ nke ukwuu bụ maka mpụta ọnọdụ mmetụta uche na-adịghị mma, nke n'aka nke ya nwere ike ịkpalite iri nri. N'ezie, nnukwu akwụkwọ nyocha na ụlọ ọgwụ na-egosi njikọ siri ike dị n'etiti mmetụta mmetụta uche na iribiga ihe ókè (Adam na Epel, 2007; Dallman, 2010), na isi ọrụ nke usoro corticotropin-releaseing factor (CRF) na-arụ (Ghitza et al., 2006; Teegarden na Bale, 2007; Cottone et al., 2009a; Warne, 2009; Shalev et al., 2010). N'okwu akọwapụtara nke ụdị anụmanụ anyị ji mee ihe ebe a, anyị egosila na mbụ na ụmụ oke ekpughere ohere ịnweta nri na-atọ ụtọ nke ukwuu, ma iri ihe ike yana ngbanwe omume na-adabere na ya (ya bụ hypophagia nke nri na-adịghị amasị ya, nchekasị ahụ. Omume dị ka omume, yana ụkọ mkpali iji nweta nri na-adịghị mma) bụ onye na-anabata ndị na-anabata CRF 1.Cottone et al., 2009a). Na mgbakwunye, mwepu site na nri dị ụtọ nke ukwuu jikọtara ya na mmụba nke CRF na etiti etiti nke amygdala, na-adabereghị na mgbake axis HPA ọ bụla, dị ka egosipụtara site na enweghị ntọhapụ corticosterone dị iche ma ọ bụ okwu CRF na paventricular nucleus. hypothalamus n'etiti njikwa na ihe ndị na-agba ịnyịnya ígwè nri (Cottone et al., 2009a). Ya mere, ọ bụ ezie na anwaleghị ya ozugbo na akwụkwọ dị ugbu a, enwere ike ịkọ nkọ na omume ịda mbà n'obi na-esite na ịnweta nri na-adịghị ala ala nwere ike bụrụ nke neuroadaptations na usoro CRF extrahypothalamic. N'ezie, usoro CRF na-emezi omume, autonomic, na endocrine nzaghachi na nrụgide, ma atụpụtawo ka ọ rụọ ọrụ dị mkpa na ọnọdụ dịgasị iche iche nke pathophysiological gụnyere nzaghachi na-adịghị mma na nrụgide, dị ka ịda mbà n'obi.Lloyd na Nemeroff, 2011). A large body of evidence, resulting from observations in both laboratory animals and humans, has pointed to the relevance of an overactive CRF/CRF1 receptor system in depression. Importantly, the anxiety-related and depression-related phenotypes that result from chronic exposure to stress in animals have been shown to be dependent on an overactive CRF1receptor system in limbic forebrain regions, including the amygdala, independent of actions of CRF on HPA axis activity (Nestler et al., 2002; Zorrilla na Koob, 2010).

mmechi

Anyị egosila na mbụ na oke ewepụrụ na nri na-atọ ụtọ na-egosi mbelata oriri nke nri chow a na-anakwere, mbelata mgbalị mkpali iji nweta nri chow, ma kwupụta omume dị ka nchegbu (Cottone et al., 2009a). Ugbu a, anyị na-agbatị nchoputa ndị a site n'igosi na ịnweta nri na-adịghị ala ala nke na-adịghị ala ala na-ebutekwa enweghi ike imegharị ihe na anhedonia, nke a na-akọwakarị dị ka omume ịda mbà n'obi.D'Souza na Markou, 2010). Enweghị ike imegharị ahụ dabere na mwepu, n'ihi na eweghachiri omume ọjọọ a site na imeghachi ohere ịnweta nri na-atọ ụtọ nke ukwuu. Nsonaazụ ndị a kwekọrọ na echiche na-ewepụ na-adịghị ala ala, ịnweta nri na-atọ ụtọ nke ukwuu na-ebute ọnọdụ na-adịghị mma.Cottone et al., 2009a, 2009b). Ya mere, iri nri mmanye nwere ike inye aka na-agwọ onwe ya na ọnọdụ mmetụta uche na-adịghị mma na-adabere na ya, dị ka nke etinyere maka mmepe nke ịṅụ ọgwụ ọjọọ.Koob na Kreek, 2007; Koob, 2008).

Nkweta

Ndị ode akwụkwọ na-ekele Stephen St Cyr maka enyemaka nka, yana Duncan Momaney na Tamara Zeric maka enyemaka nchịkọta akụkọ. Emere mbipụta a site n'aka Grant Numbers DA023680, DA030425, MH091945, MH093650A1, na AA016731 sitere na National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), na National Institute on Alcohol Abuse and Alcoholism (NIAAA). ), nke Peter Paul Career Development Prọfesọ (PC). Ihe dị n'ime ya bụ naanị ọrụ dị n'aka ndị dere ya, ọ bụghịkwa na ọ bụchaghị na-anọchite anya echiche gọọmentị nke National Institutes of Health.

Notes

Ego (na) enyemaka a kwadoro akwụkwọ a:

National Institute of Mental Health : NIMH R01 MH091945 || MH.

Ụlọ ọrụ mba na-ahụ maka ịṅụ ọgwụ ọjọọ: NIDA R01 DA030425 || DA.

Ụlọ ọrụ mba na-ahụ maka ịṅụ ọgwụ ọjọọ: NIDA R00 DA023680 || DA.

Ihe odide ala

Esemokwu mmasị

Enweghị esemokwu ọ bụla.

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