Aversive Stimuli Drive Drug Ịchọ na State nke Low Dopamine (2014)

Ọrịa Ọrịa. 2014 Sep 22. pic: S0006-3223 (14) 00703-3. doi: 10.1016 / j.biopsych.2014.09.004. RC na-ejikọta1, Wheeler DS2, Ebben AL2, Jacobsen AJ2, Robble MA2, Mantsch JR2, Wheeler RA2.

nkịtị

Mụrụ

Ndị na-ahụ maka nrụgide na-emetụta ọnọdụ mmetụta uche ma na-eme ka ọgwụ ghara ịchọrọ, n'otu akụkụ, site na nhazi nke usoro mesolimbic dopamine. O bu ihe nwute, iwu ngwa ngwa nke dopamine na-egosi site na mkpali azuma mmadu nke n’eme ka ogwu achoghi nke oma. Na usoro nke nnwale, anyị nyochara usoro dị ntakịrị nke akara dopamine site na mkpali na -akpata, quinine, ma nwalee ike ya na-akpata ịchọ cocaine. Na mgbakwunye, anyị nyochara usoro midbrain nke ihe mgbaàmà dopamine na cocaine na-achọ site na peptide na-akpata nchekasị, corticotropin na-ewepụta ihe (CRF).

ụzọ

Site na ijikọ voltaji cyclic ọsọ ọsọ na ọgwụ pharmacology, anyị nyochara nsonaazụ intrasus quinine na ntinye akarị nkwụpụta dopamine na ngosipụta hedonic na 21 ụmụ nwoke Sprague-Dawley rats. Anyị nwalere ọrụ CRF n'ịgbanwe mgbanwe na-akpata mgbanwe na mkpokoro dopamine na cocaine na-achọ site na ịnye mmadụ nkwado mmụọ CRF, CP-376395, na mpaghara ventral tegmental (VTA).

Results

Anyị chọpụtara na quinine belatara ngwa ngwa dopamine na ọkwa abụọ dị iche. Anyị kpebisiri ike na CRF mere na VTA iji dozie mbelata ya na naanị otu n'ime oge ndị a. Ọzọkwa, anyị chọpụtara na e wepụrụ mbelata dopamine ụda na coinine na-akpata cocine site na igbochi ọrụ CRF na VTA n'oge ahụmịhe nke mkpali azụ.

Mkpebi

Ihe omuma ndi a gosiputara na acho ogwu ojoo na acho ime ka onodu ojoo dopamine di ala dabere na ntinye dopamine nke CRF.

Keywords:

Ihe omume ndụ na-akpata nchekasị bụ ndị nwere ike ịgbanwe ọnọdụ ha ma nwee ike ịkpalite ọtụtụ àgwà ọjọọ, gụnyere ị abuseụ ọgwụ ọjọọ (1). Ọ bụ ezie na iri mmadụ ahụ riri ahụ bụ ọtụtụ ihe na-akpata ọrịa, a na-atụ aro na ihe omume ndụ na-egbu mmụọ nwere ike ịkwalite nlọghachi azụ na-eri ahụ site na itinye mmetụta na agụụ na-ezighị ezi2, 3, 4, 5). N'otu aka ahụ, ọgwụ metụtara ọgwụ na-akpali ọnọdụ na-adịghị mma na ndị ọrụ cocaine na-ezere na-ebu amụma nlọghachi (2, 4, 6). N'ikpeazụ, a na-eche na ihe mkpali ndị a na-akwalite mgbanwe nke akparamaagwa nke ndị na-a substanceụ ọgwụ ọjọọ, na-anwa ịhapụ ịdị na-ezere, ka a na-akpali imezi ọnọdụ ọnọdụ ọjọọ na-emetụta gburugburu ebe obibi site na ịmaliteghachi nke ọgwụ.7, 8, 9, 10, 11).

Ihe omume na-atụgharị uche na ọnọdụ mmetụta uche ha na-ekwu na ọ ga-akpalite ọgwụ ịchọrọ site na ịkagbu usoro doolamine mesolimbic, mana usoro nke ha na-eme nke a bụ nke ọma. N'ezie, n'agbanyeghị ihe akaebe na-arị elu na mmetụta na-adịghị mma bụ ihe dị oke egwu nke ịmaliteghachi ọgwụ na-esochi oge ịhapụ ị ,ụ ọgwụ, akwụkwọ ndị a na-agbagha na ajụjụ bụ isi nke nduzi nke dopamine nzaghachi na-akpali akpali (12, 13). Ọmụmụ electrophysiological na electrochemical nke na-atụ ọrụ dopamine neuron na ntọhapụ ọdụ dopamine, n'otu aka ahụ, commensurate with the sensation ozugbo na nghọta nke ngbali azụ. na-akọwapụta mbelata ngwa ngwa na akara dopamine na nzaghachi na-akpali akpali na ndị na-eburu ha amụma (14, 15, 16, 17, 18, 19). TA na-ekwu na mbelata ya na ọrụ dopaminergic kpatara, akụkụ ya, site na ndị neuromodulators na-akpata nchekasị dịka corticotropin na-ewepụta ihe (CRF) (20, 21). Ọ bụ ihe nwute, ihe ndekọ electrophysiological nke dopamine neurons na-egosi na ma Mbelata na-akpata ọrụ dopamine ma ọ bụ iwu CRF nke nzaghachi ahụ enweghị otu. (22, 23, 24, 25), chọrọ ụzọ dị iche iche nke na-enyocha akara ngosi ngwa ngwa na dopamine neuronal lekwasịrị anya iche.

Amachaghị banyere ọdịdị ngwa ngwa mgbapụta dopamine na-emetụta onwe ya na mpaghara ndị dị mkpa. Amabeghị etu mkpali dị otú a nwere ike isi mee ka mbelata dopamine na-ebelata yana otu mbelata dopamine nwere ike isi kwalite agwa ndị nwere oke ọgbụgba, dịka ịchọ ọgwụ. Na ngụkọta ngụkọta akụrụngwa (NAc), ọnọdụ dị oke mkpa nke ihe nkwụghachi ụgwọ, na-abawanye ma na-agbadata mkpokọta dopamine na-eme ka D1- na D2-receptor –ekwupụta ọkara spuine neurons (MSNs) n'otu n'otu, nke nwere mmetụta na-emegide ihe na akparamaagwa nke mmụọ. (26, 27). Arụ ọrụ nke sekit ndị a dị iche iche ka amaara nso na-achịkwa iche iche nke omume kpaliri, gụnyere mmeghachi omume nke ọgwụ ọjọọ. (28, 29, 30, 31, 32, 33). Yabụ, ịkọwapụta ma ọ bụrụ na ịgbanye ume ọkụ ga-abawanye ma ọ bụ belata mkpụ uche NAc dopamine bụ ihe dị mkpa maka ikpebi etu ihe omume ndụ siri ike na-eme ka ọ dị iche iche iji mee ka ịmaliteghachi ị drugụ ọgwụ. Na mbụ, anyị chọpụtara na ọgwụ cocaine na-ebu amụma nwere ike ime ka ọnọdụ na-adịghị mma pụta, ma n'otu oge na-ebelata akara dopamine na NAc (19). Agbanyeghị, akparamagwa omume nke ihe abụọ ndị a kwuru ka ga-elele. Ajuju ajuju banyere uzo azumahu na-edozi nsogbu izizi dopamine yana ma usoro a bu nke nwere ike iduba agwa ndi mmadu ka acho ihe banyere ogwu. N'ime ọmụmụ ihe ndị a, anyị nyochachara kpọmkwem mgbanwe nke oge ngbanwe nke mgbawa dopamine, ụkpụrụ site na mwepụta CRF nrụgide n'ime mpaghara ngalaba (VTA), yana mmetụta omume na nhazi hedonic na ịchọ ọgwụ. Na mkpokọta, nchọpụta anyị na-ekpughe ihe dị mgbagwoju anya na oge mgbaàmà dopamine yana ikike CRF ịchịkwa ụda dopamine ma kwalite ọgwụ ọgwụ.

Andzọ na Akụrụngwa

Ndị isi

Tsmụ nwoke Sprague-Dawley ụmụ nwoke iri abụọ na otu (275 – 300 g; Harlan Laboratories, St. Louis, Missouri) nọ n'otu ebe na-ekpo ọkụ ma na-achịkwa udu mmiri, Association maka Ntụle na Nnabata nke Nlekọta Anụmanụ Anụmanụ nyere vivarium. Ejiri oke dị na 12 / 12-hour okirikiri mgbagharị (ọkụ na 7 am) ma nwee mgbasa ozi libitum (belụsọ ma edepụtara) na mmiri na nri (Teklad; Harlan Laboratories). Kọmitii Nlekọta Anụmanụ na Nlekọta Anụmanụ na Mahadum Marquette kwadoro nnwale ndị nnwale niile na Nlekọta Instlọ Akwụkwọ nke Ahụike Ahụike maka Nlekọta na Ojiji nke anụmanụ.

 Ịwa ahụ

Emere usoro ịwa ahụ niile n'okpuru ọgwụ ketamine / xylazine (100 mg / kg / 20 mg / kg, intraperitoneal). A kpụbara intrajugular intrajugular catheter dịka akọwapụtara na mbụ (11). A na-etinye ntinye akwụkwọ ntuziaka maka microinjections (26-gauge; Plastics One, Roanoke, Virginia) ka etinyere ya na ntanetị ozugbo ozugbo na VTA (isi-posta: −5.6; medial-lateral: ± 2.2 na 11le n'akuku; dorsal-ventral: NUM7.0). Iji kwadebe maka ndekọ ọkụ ọkụ, a na-etinye cannulas ndu electrode karịa NAc shei na-enweghị otu (isi ihu: + 1.3; medial-lateral: ± 1.3), na etinyere igwe elektrọnik ọlaọcha / ọlaọcha na ntuziaka cannula. Ọzọkwa, ihe mgbakwunye na-akpali akpali nke electrode / microinjection guide cannula (Plastics One) bụ nke etinyere ya ozugbo n’elu iptalateral VTA, etinyere ntuziaka cannula dị elu karịa VTA contra contraition. Maka usoro ịwa ahụ niile, a na-emeso oke iji ọgwụ mgbochi mkpali (1% ọnụ nkwusi) ụbọchị na maka ụbọchị 2 na-esochi ịwa ahụ iji belata mbufụt na mgbu mgbe akwara. Iji nọgide na-enwe ikikere, a na-eji mmiri gbara itiri (intraatun) ma ọ bụ saline heparinized na ọgwụ mgbochi cephazolin (intravenous [IV]), na-agbapụ intraatun na intrajugular catheters kwa ụbọchị.

Microinjections

Microinjectors gbatịrị .5 mm site na njedebe nke ntuziaka cannula. Ọkpụkpụ akpụ akpụ akpụ (aCSF) (.3 µL / min) ma ọ bụ onye na-ahọta CRF receptor antagonist CP-376395 (.3 µg / .3 biL / min) ka abatagoro na VTA (n = 6 aCSF, n = 6 CP-376395). CP-376395 bụ onye na-atụgharị uche CRF-R1, mana mmekorita ya na R2 nwere ike ịbụ na usoro a. A hapụrụ microinjectors n'ọnọdụ maka nkeji 2 mgbe ogwu gachara iji nye ohere ngbasa. N'ime usoro abụọ a, a na-ebugharị nnyefe quinine ozugbo ogwu ogbugba.

Egwuregwu Voltammetric

Mgbe ọ gbakechara n'ịwa ahụ, oke na-anọrịrị elekere maka oge 2 na gburugburu ebe a na - egwu ọkụ, na - enwe ụlọ Plexiglas doro anya (Med Associates, St. Albans, Vermont) debere n'ụlọ ndozi Faraday emeziri. Edebere VTA na-akpali akpali na kọmpụta na-atụgharị (Crist Instrument Co., Hagerstown, Maryland), na otu intraoral cannula ka a na-agbanye na mmiri na-agbanwe (Instlọ nyocha Nkụzi, Nzukọ Plymouth, Pennsylvania) nke nwere ike ịnweta mmiri si na sirinji sirinji (Razel , St. Albans, Vermont). N'echi ya, a na-eme ndekọ ọkụ ọkụ dị ka akọwara na mbụ (16). Nkọwa nke usoro ndekọ na nyocha ka akọwara n’ime Ntinye 1. Na nkenke, a wedatara carbon fiber electrode na shei NAc, a na-etinye eriri mmiri na intraatun cannula, a na-amalite nnọkọ omume. Nnwale ahụ nwere usoro nlekota dopamine nkeji oge 30 (usoro 1); oge nnyefe Quinine nke oge 30 (frasi 2); biin VTA microinjections abụọ na oge nnyefe quinine nkeji oge 50 nkeji oge (usoro 3). N'ime oge nnyefe quinine, a na-eweta 6-nke abụọ nke .2 mL quinine (.001 mmol / L) ihe dị ka nkeji ọ bụla.

Nnyocha data Voltammetry

A kọwara nkọwapụta nyocha nke Ntinye 1. Edekọtara data sitere na nnwale nke ọ bụla (−20 sekọnd na 30 sec postinfusion) site na iji 1-Second block na minima mpaghara dị na sekọnd 20 tupu mmalite. Maka mpịkọ nke ọ bụla, a gụkọtara ọnụ data n'ofe quinine infusion na 10 sekọndị na mmalite nke oge infinine infinine (quinine) ma e jiri ya tụnyere 10-nke abụọ (prequinine) na nke abụọ nke 10-nke abụọ (postquinine). E nyochara nsonaazụ nke ugbu a ka oge na-aga maka mgbanwe dopamine site na iji usoro nnabata. Niile maka oke (n = 12), mbelata nke pụtara onwe ya (anaghị agbachi oge) ụda dopamine ka a tụlere ma tulee ya site na atule ọnwụnwa mbụ nke 5 (na mbido) na ule 11 na 15 (etiti) na ọnwụnwa ikpeazụ nke 5 (mbubreyo) n'oge prequinine , 10 sekọnd tupu mkpata quinine, na-eji nyocha ugboro ugboro nke iche (ANOVA). A na-enyocha mgbanwe ndị dị ukwuu na mkpokọta dopamine oge, na-agbachi oge quinine infusion site na iji usoro abụọ n'ime-usoro ugboro ugboro ANOVA na-agbanwe usoro (isi, quinine, na quinine + ọgwụ [aCSF ma ọ bụ CP-376395]) × oge (prequinine, quinine, postquinine). Mgbe achọpụtara mmetụta dị mkpa ma ọ bụ mmekọrịta, a na-eji ntụnyere ụzọ abụọ na ule hokey nke Tukey maka ọtụtụ ntụnyere na alfa setịpụrụ na .05.

Ihe omume Dopamine mere na nnwere onwe na nke ọ bụla etinyere ma ọ bụ nnwale na-achịkwa akparamagwa akụrụngwa n'oge oge. Iji chọpụta otu ihe mkpali sitere na ntanetị metụtara ihe omume dopamine ịta ọkwa, ihe ngosi 100-msec na ọnwụnwa ọ bụla maka oke ọ bụla ka nwere oge ma ọ bụrụ na ntinye ya bụ 40 nmol / L ma ọ bụ karịa. Thzọ a dị n'etiti ụdị nke maka ndị na-anabata D1 dị elu ma bụrụ uru nkezi nke ihe omume dopamine n'etinye oge (34, 35). Site na njirimara a, a na-amata ma na-atụle ugboro ugboro ugboro. Ejiri ANOVA ụzọ abụọ mee ihe iji mata isi ihe oge (quinine dipo postquinine) na ọgwụ (aCSF vs. CP-376395). Ejiri Tukey nyocha post hoc maka ọtụtụ ntụle iji chọpụta ọdịiche dị mkpa n'etiti oge na ọgwụ. N'okwu niile, ọkwa alfa maka ihe dị mkpa .05. Ejiri atụnyere Statistical site na iji sọmịahịa dịnụ (Statistica; StatSoft, Tulsa, Oklahoma).

Nnyocha Ihe Nnyocha Ihe Ọrụ

A tụlere ọrụ retegritiki na epeepe-na-ekule na iji vidiyo dijitalụ edekọ n’ụbọchị ule na ntụpọ aCSF- na CP-376395 (n = 5 na otu ọ bụla). Agụụ agụụ na aversive uto a gụrụ na prequinine na quinine oge jiri usoro nke Grill na Norgren (36). A na-agụta agagharị agagharị nke kwekọrọ n'ụdị triangle maka oge karịrị 90 msec dị ka azagharị. Usoro ndị a ka ewepụrụ otu ihe na-anọpụ iche na mmegharị ọnụ na agagharị, bụ nke a gụrụ dị iche. Udiri edebere edegara ma gafere n'etiti ahuru na ntukwasi obi. A na-ahụta omume liche fọdụrụ ka ọpụpụ iche. Ejiri nyocha data ndekọ akparamagụ niile emere site na sọftụalụ dịnụ (Statistica).

Nchịkwa Onwe Gị na Nnabata

A zụrụ oke dị nfe na-adịghị nwayọọ (15-18 g / ụbọchị) ka ịpịa lever maka pellets sucrose. Mgbe nnweta nke lever na ịpị (~ 3-5 ụbọchị), intraoral na intravenous catheters ka etinyere dị ka akọwara n'elu. Mgbe a gbakechara, a machibidoro oke nri nri ọzọ ma zụọ ya ka ọ na-achịkwa cocaine (.3 mg / .2 mL / infusion, IV) na nhazi oge 1 dị na kọmpụta na-arụ ọrụ na kọmputa na-ejikọ ọnụ na cubicles na-ada ụda (Med Ndị mmekọ) Mgbe usoro cocaine malitere, ọkụ ụlọ na-enwu n'ime ụlọ ahụ, ọkụ ọkụ dị n'elu onye na-arụ ọrụ na-egosi na cocaine dị. Ihe ọ bụla cocaine na-esonyere site na ịgbanyụ ọkụ ụlọ na ọkụ ọkụ, na oge nkwụsị oge na-adịgide 20 sec, n'oge nke a na-edeba ihe na-aza ya ma dekọọ nzaghachi mana enyeghị nkwado. Edeghachikwara nzaghachi nke abụọ na-adịghị arụ ọrụ. Mgbe oge ịkwụsị, ọkụ ụlọ na ọkụ ọkụ agbanwuru ma gosipụta na cocaine dị. Oge nchịkwa onwe onye mere na usoro usoro ihe omume anọ na-achịkwa ụbọchị isii nke nwere ụbọchị 6 nke nchịkwa onwe onye cocaine na ụbọchị 3 na-enweghị cocaine n'ime oghere ụlọ. Mgbe usoro nke atọ gasịrị, ụmụ oke niile natara ịwa ahụ canta nke VTA wee malite usoro nke anọ ha mgbe izu 3 gachara. Oge cocaine ọ bụla na-akwụsị mgbe oke na-enweta ọnụọgụ kachasị nke cocaine infusions (2 infusions maka ụbọchị 25 mbụ nke ịnweta tupu VTA cannulation na 9 infusions maka ikpeazụ cocaine sessions na-eso VTA cannulation). Mkpochapu bu nke oge 30 nke ubochi nke oge obula nke obula na-ebute nnu nnu ma o nweghi ihe ngosi ma obu inye aka cocaine. Ozugbo a kpochapụrụ njirimara njedebe (<2 nzaghachi na-arụsi ọrụ ike maka njedebe ụbọchị 15; S1 SX in Ntinye 1), nwale ọ bụla ka nwalere maka inwetaghachị ya maka iji nweta nkwụghachi nke quinine. Iji gbochie oke mmetuta nke nwute, a na - eme nyocha maka anụmanụ ọ bụla ụbọchị e mechara nhapụta mkpochapụ. Tupu nnọkọ mmalite ọ bụla, òké natara microinjections intra-VTA nke aCSF (n = 4) ma ọ bụ CP-376395 (n = 5). Oge nloghachi bidoro site na 15 intraoral infusions nke quinine ewepụtara na ụlọ nchịkwa cocaine n'otu ụzọ ahụ na nnwale gara aga maka nkeji 15. Nkeji ise mgbe nnyefe quinine, a na-agbatị ndị levers ma na-aza nzaghachi maka awa 1.

Nnyocha data nyocha

A tụlere mgbanwe mgbanwe omume na elekere mbụ nke nnọkọ ọ bụla site na iji ụzọ abụọ ANOVA na-agbanwe ihe dị n’etiti ọgwụ ọgwụ (aCSF, CP-376395) factor ihe dị n’ime nke ụbọchị (mkpochapụ, iweghachite, iweghachi azụ) . A kọwara nzaghachi mkpochapụ dị ka ụbọchị ikpeazụ nke ọzụzụ ikpochapu, azịza nzaghachi posta bụ nnọkọ ikpeazụ nke a nwalere n'okpuru ọnọdụ mkpochapụ enweghị nchịkwa quinine. Achọpụtara ọdịiche dị mkpa na omume ịchọ ọgwụ ọjọọ mgbe ekwesịrị ekwesịrị ule nyocha nke hokey Tukey maka ọtụtụ ntụnyere na alfa setịpụrụ na .05.

Historyology

Mgbe emechara usoro nyocha, ihe ndị metụtara isiokwu jupụtara na carbon dioxide. Iji chọpụta ebe a na-edekọ ihe ndị na-eme ndekọ, e mepụtara obere ọnya electrolytic site na ịhazi ihe dị ugbu a (250 µA) site na igwe anaghị agba nchara igwe etinye na omimi ebe ndekọ ahụ mere. A wepụrụ ụbụrụ ma maa emikpu na 10% formaldehyde maka ụbọchị 14. E mesịa wee kewaa ha n'ime akụkụ 40-,m, etinyere ya, jiri ntụpọ .25% wee kpuchie. A na-egosi ntụnye nke ebe cannula na electrode site na voltametry na nnabata nnabata S1 isi na S2 in Ntinye 1, n'otu n'otu (37).

Results

Iji nyocha ọnọdụ mgbanwe nke ọghọm dopamine na-akpata site na ihe omume na-emetụta anyị, anyị were ọkụ ọkụ na-enyocha ngwangwa ngwangwa na-agagharị na oke nke intraoral infusions nke enweghị mkpasu iwe, na-elu ilu nke quinine. Ihe ngosi a na-enye ohere maka inyocha onodu ihe imekorita nke anumanu na ntule nke mweputara dopamine na NAc.16, 19). Dịka a tụrụ anya, n'ofe ule nkeji nke 30 (1 infusion / min), ekpughere quinine kpalitere ngosipụta nke mmeghachi ahụ uto averes oge a na-akpọchi iji belata mbupute dopamine ọnụ (Nyocha 1B; oge 2, prequinine ma e jiri ya tụnyere oge quinine / postquinine, aka ekpe na aka nri; S3 dị na ya in Ntinye 1). N’ụzọ na-atụ n’anya, mbelata dopamine gosipụtara mkpụrụ akwụkwọ abụọ oge ụfọdụ na-apụtachaghị ìhè: pụtara ozugbo, ọdịda dị obere n’oge ọ bụla igosipụta quinine, yana mbelata ogologo oge na ụda dopamine nke na-apụta naanị mgbe ekpughere ugboro ugboro na quinine. A tụlere nsonaazụ nke ikpeazụ a dị ka mbelata dị ukwuu n'etiti (ọnwụnwa 11 – 15) na mbubreyo (ọnwụnwa 26 – 30), ma e jiri ya tụnyere ọnwụnwa mbụ (5 mbụ) na prequinine oge 10 sekọnd tupu quinine infusion (Nyocha 1B, n'aka nri). Ihe omuma ndi a n’egosi ike nke nkpagbu iwelata dopamine ebe ekpughere ihe banyere oge nzaghachi a.

Foto ntanetị nke Foto 1. Mepee nnukwu ihe oyiyi    

Nyocha 1

Corticotropin na-ewepụta ihe na - egbochi ọgbụgba dopamine n'oge ahụmịhe nke mkpali ihe na - enweghị atụ. (A) Mgbanwe ndị nọchitere anya na ntinye uche dopamine na-ahụkarị na shei nke akwara dị na njikwa na -eme ihe (aka ekpe) yana nnwale (aka nri) na usoro ịtọ (usoro 1). (B) Mgbanwe dopamine gbanwere na nzaghachi na intraoral management nke quinine (frasi 2). Enwere ike ịhụbelata mbelata ihe niile na nzaghachi quinine (x axis) na kwa n'ofe ọnwụnwa (y axis, prequinine [Pre Q]). (B) (n'isi aka nri) Inye akwara intanoral nke quinine belata donic dopamine lekọtara n'ofe ikpe dị na oge prequinine nke usoro 2 (nyocha nke isi ihe dị iche iche: ọnwụnwa F2,22 = 11.73, p <.01; Tukey zigara hoc, *p <.05, oke mbelata na etiti na ngwụcha ọnwụnwa ma e jiri ya tụnyere ule mbụ). (C) Mbelata mkpata Quinine na akara dopamine site na injections ngalaba nke intraventral nke ngalaba nke corticotropin na-ewepụta ihe antagonist, CP-376395 (frasi 3). aCSF, mmiri ara nwa; DA, dopamine; Post Q, postquinine.

Ayi juru aju ma nbido nke dopamine a nke CRD na VTA neme ya.21). Na oge 3, ụmụ anụmanụ natara intin-VTA microinjections nke CRF antagonist CP-376395 (.3 µg / .3 µL / min) ma ọ bụ aCSF (.3 µL / min), ebe nnyefe intrasus quinine na ngwa ngwa ịdekọ ngwa ngwa cyclic voltametry ngwa ngwa (Nyocha 1C, n'aka nri; S1 dị na ya in Ntinye 1). Ntughari CRF na VTA enweghi mmetuta na ikike nke quinine iji mee ka mbelata dopamine ngwa ngwa, dị mkpụmkpụ n'oge oge mkpịsị intraoral infusion.Nyocha 1C). N'ụzọ dị iche, antagonism CRF na VTA kagburu mmetụta nke quinine na ụda dopamine na-enweghị oge akpọchi n'oge prequinine na postquinine oge (Nyocha 1C). Site na ịgabiga ule niile, enwere ike ịche itinye uche dopamine oge.Ihe osise 2A, B), tinyere nnukwu mbelata na-esite na infinine infusion. Enwere ike iji anya nke uche hụ ihe mmeghachi omume a na-eso nkwenye CRF (Nyocha 2D) na nyochajupụtara usoro nyocha nke kemịkalụ (Ihe osise 3A, B).

Foto ntanetị nke Foto 2. Mepee nnukwu ihe oyiyi    

Nyocha 2

Oge ntinye uche dopamine na-agbanwe n'oge ntinye quinine na ịgbaso corticotropin na-ewepụta ihe nnabata ihe nnabata. Ihe ngosi agba agba nke okpukpu abuo nke ihe omuma ihe omimi nke cyclic anakọtara maka 50 sekọnd gburugburu infusin quinine, na-agbadata ule niile maka usoro nke ọ bụla. Elektrik bụ volta etinyere (Eapp) na abscissa bụ oge (sekọnd [s]). A na-egosipụta mgbanwe na ugbu a na carbon carbon electrode na agba. Na oge 2, infinine infusion belatara ntinye uche dopamine oge na njikwa (A) na nnwale (B) ụmụ anụmanụ. (C) Mbelata a dịgidere na òké ndị na-enweta ọnya mmiri ara dị ka mmadụ (aCSF) na-aga n'akụkụ mpaghara ventral. (D) Mgbakwunye mgbochi nke corticotropin na-ewepụta ihe mgbapụta CP-376395 nyochaghachiri mbelata a. Ahịrị kwụ ọtọ na-egosi oge a na-echepụta atụmatụ cyclic voltaji iji gosi ọnụnọ dopamine (n'aka ekpe), mbelata ya site na quinine (etiti), na mgbanwe pH na-eso infusion mkpali intraoral (n'aka nri).

Foto ntanetị nke Foto 3. Mepee nnukwu ihe oyiyi    

Nyocha 3

Ntinye intrasus nke uto aversive, quinine, belata itinye uche dopamine na corticotropin na-ewepụta ihe na-adabere. Mgbanwe mgbanwe mkpokọ dopamine (DA), kpebisiri ike site na nyocha nke ihe bụ isi (A) na (B) (A) Quinine belatara dopamine ịba uru nke ukwuu site na usoro (1 frasi) na ụzarị ọnya nwa (aCSF) -apụtara (nyocha nke oge mgbanwe dịgasị iche iche; F4,20 = 10.683, p <.001; Tukey zigara hoc, *p <.05). (B) Mbelata dopamine nke Quinine ka agbakwunyere na oke oke-arụ nke CP-376395 (nyocha nke oge mgbanwe iche iche × ọgwụ mmekọrịta; F4,20 = 6.77, p <.01; Tukey zigara hoc, *p <.05, mbelata dị ukwuu na ụmụ anụmanụ na-agwọ ọrịa CP-376395 naanị na oge quinine). Ntughari dopamine gbanwere site na injections injections nke CP-376395 ma naanị na prequinine (Pre-Q) na postquinine (Post-Q) oge nke quinine na-anọghị. E gosipụtara data dị ka pụtara + SEM.

Mgbanwe ngbasa ozi dopamine n'ịkpa ụmụ anụmanụ nwere ike iburu mgbanwe site na ugboro ugboro ma ọ bụ njupụta nke ihe omume dopamine (38). N'ebe a, anyị chọpụtara na quinine belatara ụda dopamine site na ịbelata ugboro ole a ga-ahapụ ya, na agbanwere mmetụta a site na igbochi ndị na-anabata CRF na VTA (Nyocha 4A). N'ịchịkọtara, data ndị a na-egosi na na mkpali iwe, CRF na-egosi na VTA na-egbochi ụda dopamine na NAc site na ịmegharị ugboro ole ihe omume dopamine tọhapụrụ.

Foto ntanetị nke Foto 4. Mepee nnukwu ihe oyiyi    

Nyocha 4

Quinine belatara ugboro ole ihe ịhapụ dopamine. (A) Ihe mkpalite Quinine na-ebelata belata oge nke dopamine na oge na-esochi njikọta intrasus, mmetụta a wezigharịrị na usoro corticotropin na-atọhapụ mmiri mmiri mmiri (aCSF) mgbe ejiri ya na postCinine ACSF (F1,10 = 10.21, Tukey post hoc, *p <.05]. (B) Ngwakọta quinine enweghi mmetụta na ntọhapụ nhapụta n'otu oge (F1,10 = .75, p > .05) E gosipụtara data dị ka pụtara + SEM.

Aversive akpali ike ịchịkwa ọ bụghị naanị na emetụta ọnọdụ kamakwa maladaptive kpaliri omume nke ọgwụ ọjọọ (3, 9, 39, 40), nke a na njikọ chiri anya na ịdọ aka na etiti dopamine (41, 42ma CRF na-ahazi ya.43, 44, 45, 46). Anyị nwalere ma ekpughe ọnụnọ quinine na onye na-eso ya na NAc dopamine zuru oke iji chụpụ ọgwụ n'ịchọ ọgwụ n'ọnọdụ iweghachị azụ. A zụrụ azụ maka oke iji pịa onye na-enye ọgwụ maka III cocaine infusion. Mgbe oge nchịkwa onwe kwụsiri ike, akụrụngwa akụrụngwa ahụ na-akwụsị site na ịkwụsị ị availabilityụ koken. Mbechachara, oke raara infusions intrasus quisine impressis (1 infusion / min maka nkeji 15) sochiri ohere ịpịpụta lever ahụ nke nyeburu cocaine na mbụ. Nchịkwa Quinine mụbara lever na-agbanye naanị onye na-arụ ọrụ (Nyocha 5A; S4 dị na ya in Ntinye 1), iji gosipụta mkpali na - egbochi mmụọ dopamine nwekwara ike ịmaliteghachi omume ịchọ ọgwụ. Ọzọkwa, omume iweghachite ya zuru oke site na igbochi ndị na-anabata CRF na VTA (Nyocha 5A; S2 dị na ya in Ntinye 1). N'ụzọ na-adọrọ mmasị, ọ bụ ezie na CRF emegideghị ihe na-egbochi omume iweghachi, ọ na-egbochi ikike ichebe onwe nke quinine, dị ka ngosipụta na-adịgide adịgide nke mmeghachi ahụ ụtọ uto.Nyocha 5B). Ejikọtara ọnụ, data ndị a na-egosi na mkpali iwe na-egbochi ụda dopamine nwekwara ike ịmaliteghachi omume na-achọ ọgwụ ọjọọ ma a na-egbochi omume abụọ a site na igbochi ndị na-anabata CRF na VTA.

Foto ntanetị nke Foto 5. Mepee nnukwu ihe oyiyi    

Nyocha 5

A na - achịkwa usoro mkpali, mana ọbụghị okwu metụtara okwu metụtara corticotropin. (A) Mkpochapu (Ext), intraoral infusions nke quinine kpatara cocaine na-achọ na nnwale nnụnwụ (Rein) na oke mmiri artbrospinal mmiri (aCSF) na-agwọ ọrịa, mmetụta nke tụgharịrị site na mpaghara injections nke CP-376395 (nyocha nke ọgwụ dịgasị iche Mkparịta ụka ụbọchị; F2,16 = 5.83, p <.05; Tukey zigara hoc, *p <.05). (B) Ntinye intrasus nke uto aversive, quinine, mere ka ngosipụta nke mmeghachi ahụ uto aversive na òké aCSF mesoro. Edegharịghị mmetụta a site na nsị mpaghara mpaghara intraventral nke ngalaba nke CP-376395 (t1,9 = .98, p > .05) E gosipụtara data dị ka pụtara + SEM. Post, postquinine.

Nkwurịta

Akuko a gosiputara uzo nke azuma mmadu nke nwere ike igbapu ihe nkwali iji kwalite omume icho ogwu. Mkpịsị akwara intrathing nke aversive tastant, quinine, kpatara mbelata ma mbelata nrịanrịa akara akara dopamine (ya bụ, mbelata n'ofe sekọnd na nkeji gafere). Nkwupụta ndị gara aga akọwaala ngwa ngwa, mbelata nke mbelata, na-akpata mgbada na dopamine (16). Agbanyeghị, na enweghị nnweta mkpagharị ozugbo, enwere ike ịhapụ ihe ndị na-eme ka ọ bụrụ ihe mgbaàmà tonic na nkeji oge.47). Site na iji usoro a, anyị chọpụtara na cocaine na-ebu amụma nwere ike ime ka mmetụta na-adịghị mma ma n'otu oge na-ebelata ma akara abụọ nke phasic na tonic dopamine na NAc. (19). N'ụzọ na-akpali mmasị, anyị chọpụtara na tonic, mana ọ bụghị nke nnwapụta, na-agbanwegharị site na igbochi ndị na-anabata CRF na VTA. Ọ bụ ezie na mmachi a emetụtaghị ihe ndị a na - ahụ anya nke quinine, ọ na - agbanwe ọgwụ cocaine na - akpata quinine, na - egosipụta na mkpali na - eme ka mmadụ nwee ike ịkwụsị ọgwụ ị inụ ọgwụ na ọnọdụ dopamine dị ala. Ọmụmụ ihe ndị ọzọ ga-adị mkpa iji kọwaa ma sistemụ na uru omume nwere ike ịdị na mbelata dosamine na nzaghachi nke mmeghachi ahụ.

Ihe nchoputa a gosiputara odi nkpa ichota uzo ihe doro anya site na nke na - ewepu ihe na - eme ihe omume na --aghari ime ihe omume, na - ebuli nrịba ama nke dopamine na onodu ụfọdụ ma wedata akara dopamine na ndi ozo. Dịka ọmụmaatụ, e gosipụtara footshock elektrik na-eme ka CRF dịkwuo elu na VTA (45, 46), nke, n'aka nke ya, nwere ike iwelie ọrụ dopamine neuron (25, 44, 45, 48) nanabataghachị ọgwụ ịchọrọ (43, 45, 46). Ọ bụ ezie na nchoputa ndị a yiri ihe na-emegide na akụkọ dị ugbu a, ha na-agbanwe agbanwe na usoro dopamine na-egosi site na iji microdialysis nke na-akọkarị mkpali na ntinye uche dopamine ọtụtụ oge n'oge na mgbe ọ gbasasịrị ume na-akwalite ịchọ olulu. (49, 50, 51, 52). Tdata ọ dị ugbu a na-akpali agụụ mmekọahụ n'ihi na ha gosipụtara na mkpali na-ebelata ibelata akara ngosipụta dopamine nwekwara ike kwalite ịchọ ọgwụ nakwa na ihe abụọ ahụ dị n'okpuru aka CRF.

Otu nkọwa ga - ekwe omume maka otu esi abawanye ma belata na akara dopamine nwere ike ibute ịchọ ọgwụ ọgwụ nwere ike ịchọta n'ọgbakọ nzukọ nke mpaghara dopamine.

A na-ekiri ọnụ ọgụgụ ọghọm dị iche iche nke neuron dị iche iche na -eche iche ma ọ bụrụ na-abawanye ma ọ bụ ibelata mkpokọta dopamine.

  • N’ime ogwe uzo dorsal, obere D1-nnabata-na-ekwupụta MSNs nke jikọtara ọnụ ụzọ ọpụpụ ụgbọala si arụ ọrụ na-eme ka ịdị elu nke dopamine na-akwalite ije ije afọ ofufo.
  • N'otu aka ahụ, D2-nnabata-na-ekwupụta MSNs, na-enwe ụzọ nrụpụta arụ ọrụ na-apụtaghị ìhè, na-egbochi ụda dopamine dị elu mana enwere mmetụta, ma na-arụ ọrụ, usoro nkwụsịtụ dopamine na-egbochi omume [maka nyocha, hụ (26)].

TNke a bụ ihe akaebe na-egosi na nzukọ a yikarịrị na ọkwa dị egwu na ventral striatum. Na NAc, usoro phasic na mgbaàmà dopamine na-eme ka nnabata dopamine nnabata-na-ekwupụta MSNs na-akwalite mmụta ụgwọ ọrụ.

N'aka nke ọzọ, mbelata na mgbaàmà dopamine na-eme ka nnabata dopamine nnabata-na-ekwupụta MSN ma kwalite mkpesa (27, 30, 53).

N'ime ihe ọmụmụ ugbu a, o nwere ike ịbụ na quinine na-emegharị nke abụọ ahụ, na-eje ozi dị ka nrụgide gburugburu ebe obibi nke belata akara ngosi dopamine ma dabere n'ịchọ ọgwụ.. Ihe ndị ọzọ metụtara gburugburu ebe obibi nwere ike ịbawanye akara dopamine na NAc ma nwee ike ibute nsonaazụ otu omume ahụ site na itinye aka na sekit dị iche iche.

NAc dopamine akara aka emetụtalarị n’ụzọ ndị na-akwalite iri mmadụ ahụ riri ahụ. NAc dopamine dị mkpa maka mmụta na-emetụta ụgwọ ọrụ (54) na azịza kwesịrị ekwesị nye ihe agbamume (55), na-akwado echiche nke akara dopamine na-enye mkpali maka ma ọ bụ stampụ na mkpali nke mkpali ume.42) ma na-atụnye ụtụ maka ịchọ ọgwụ ọjọọ.41, 56).

N'ịnakwere nke a, ọ nwere ike bụrụ ihe echebara eche n'echiche dopamine-na-ebuli ihe mkpali na-akpata ịchọrọ ọgwụ mana ọ ga-esiri gị ike iche n'echiche otu mmụọ mkpali na-ebelata akara ngosipụta dopamine si emezu nke a.

Agbanyeghị, ụfọdụ n'ime echiche izizi nke iji ọgwụ eme ihe na-atụ aro ka usoro iwepụ ọgwụ ọjọọ site na usoro nkwado na-adịghị mma iji kwalite nlọghachi nke ndị na-eri ihe na-anwa ịnọgide na-ezere (57, 58, 59). Ọ bụ ezie na ule ndị sochirinụ nke echiche ndị a jụrụ ajụjụ ma nnukwu iwepụ ego nwere ike iso na-akpata ọrịa kpatara nlọghachi oge na-adịghị ala ala mgbe ogologo oge ịinụ ọgwụ ọjọọ (60, 61, 62, 63), usoro ihe eji eme ka ihe na - akwado adịghị mma nwere ọrụ.

Ìgwè ndị nwere ọrịa neuroadaptations na-eso iji ọgwụ na-adịghị ala ala ma na-akwalite ụgwọ ọrụ insensitivity na ndidi (7, 56, 64, 65, 66) nwere ike ime ka nghọta nke ndị na - akpata nrụgide gburugburu ebe obibi bụrụ ihe ọzọ dị mkpa n'ịkwalite nlọghachị na ọnụ ọgụgụ ndị na - adịghị ọgwụ ọjọọ.

IN’ezie, ọbụnadị nke nchịkwa cocaine na-ruo nwa oge yiri ka ọ na-emetụta mmesi ike na-adịghị mma site n’aka mgbaàmà dopamine. Ka ntinye uche dopamine dara, njikwa onwe onye ga-amaliteghachi ma ụmụ anụmanụ na-enye onyinye cocaine ka ị nwee ike nwee uche ịkwụ ụgwọ dopamine chọrọ. (67, 68). N'oge nchịkwa onwe ya, ụmụ anụmanụ nwere ike mụta imeghachi omume iji zere ọnọdụ dopamine dị ala, na nsonaazụ nke mmụta a na-adịghị mma nwere ike imecha site na mkpali ịgbanye ụda dopamine dị ala. Akụkọ dị ugbu a na-egosipụta usoro nwere ike dopaminergic usoro nke usoro mkpali a na-emetụta CRF, neuromodulator nke nrụgide.

Mkpali na-eme ka a ghara idozi dopamine, na-etinye usoro a na ọnọdụ mmetụta uche ya (dịka, mmetụta na-adịghị mma ma ọ bụ na-achọsi ike) na enweghị ọgwụ adịghị. N'ezie, nchoputa ugbu a na-egosi na ndị na-eri ọgwụ ọjọọ eme ihe na-amụta imezi mbelata mgbakasị nrụgide na akara dopamine n'ụzọ kachasị arụ ọrụ site na ị coụ cocaine.

Nkwuputa na Nkọwa

Ndị ọrụ US Health Institut of Health (R01-DA015758, JRM, na R00-DA025679, RAW) nyere ọrụ a.

Anyi na-ekele M. Gilmartin, M. Blackmore, P. Gasser, J. Evans, na E. Hebron maka ntinye aka na ihe odide ahụ.

Ndị edemede kwupụtara enweghị ego gbasara ọgwụ ma ọ bụ esemokwu nke mmasị.

Mmepe Nke A. Nke Mmebe

References

  1. Òtù Na-ahụ Maka Ọrịa Ụmụaka Amerịka. Diagnostic na Statistical Manual of Mkpụrụ Ọrịa. Nke 5. Psytù Na-ahụ Maka Ọrịa Uche America, Arlington, VA; 2013
  2. Paliwal, P., Hyman, SM, na Sinha, R. Agụụ na-ekwupụta oge ịlaghachi azụ ọgwụ: Ntinyekwu nke ugbu a na ụdị Brief nke ajụjụ cocaine na-achọsi ike. Mmanya na-aba n’anya. 2008; 93: 252 – 259
  3. Lee na Nkeji edemede
  4. | nkịtị
  5. | Ederede zuru ezu
  6. | PDF zuru ezu
  7. | PubMed
  8. | Scopus (56)
  9. Lee na Nkeji edemede
  10. | CrossRef
  11. | PubMed
  12. | Scopus (240)
  13. Lee na Nkeji edemede
  14. | CrossRef
  15. | PubMed
  16. | Scopus (247)
  17. Lee na Nkeji edemede
  18. | CrossRef
  19. | PubMed
  20. | Scopus (176)
  21. Lee na Nkeji edemede
  22. | nkịtị
  23. | Ederede zuru ezu
  24. | PDF zuru ezu
  25. | PubMed
  26. | Scopus (29)
  27. Lee na Nkeji edemede
  28. | CrossRef
  29. | PubMed
  30. | Scopus (389)
  31. Lee na Nkeji edemede
  32. | CrossRef
  33. | PubMed
  34. | Scopus (1)
  35. Lee na Nkeji edemede
  36. | CrossRef
  37. | PubMed
  38. | Scopus (521)
  39. Lee na Nkeji edemede
  40. | CrossRef
  41. | PubMed
  42. | Scopus (62)
  43. Lee na Nkeji edemede
  44. | nkịtị
  45. | Ederede zuru ezu
  46. | PDF zuru ezu
  47. | PubMed
  48. | Scopus (67)
  49. Lee na Nkeji edemede
  50. | CrossRef
  51. | PubMed
  52. | Scopus (50)
  53. Lee na Nkeji edemede
  54. | CrossRef
  55. | PubMed
  56. | Scopus (28)
  57. Lee na Nkeji edemede
  58. | CrossRef
  59. | PubMed
  60. | Scopus (452)
  61. Lee na Nkeji edemede
  62. | CrossRef
  63. | PubMed
  64. | Scopus (344)
  65. Lee na Nkeji edemede
  66. | CrossRef
  67. | PubMed
  68. | Scopus (116)
  69. Lee na Nkeji edemede
  70. | CrossRef
  71. | PubMed
  72. | Scopus (28)
  73. Lee na Nkeji edemede
  74. | CrossRef
  75. | PubMed
  76. | Scopus (26)
  77. Lee na Nkeji edemede
  78. | nkịtị
  79. | Ederede zuru ezu
  80. | PDF zuru ezu
  81. | PubMed
  82. | Scopus (35)
  83. Lee na Nkeji edemede
  84. | CrossRef
  85. | PubMed
  86. | Scopus (23)
  87. Lee na Nkeji edemede
  88. | CrossRef
  89. | PubMed
  90. | Scopus (9)
  91. Lee na Nkeji edemede
  92. | CrossRef
  93. | PubMed
  94. | Scopus (215)
  95. Lee na Nkeji edemede
  96. | CrossRef
  97. | PubMed
  98. | Scopus (331)
  99. Lee na Nkeji edemede
  100. | CrossRef
  101. | PubMed
  102. | Scopus (67)
  103. Lee na Nkeji edemede
  104. | CrossRef
  105. | PubMed
  106. | Scopus (92)
  107. Lee na Nkeji edemede
  108. | nkịtị
  109. | Ederede zuru ezu
  110. | PDF zuru ezu
  111. | PubMed
  112. | Scopus (341)
  113. Lee na Nkeji edemede
  114. | CrossRef
  115. | PubMed
  116. | Scopus (3)
  117. Lee na Nkeji edemede
  118. | CrossRef
  119. | PubMed
  120. | Scopus (146)
  121. Lee na Nkeji edemede
  122. | CrossRef
  123. | PubMed
  124. | Scopus (99)
  125. Lee na Nkeji edemede
  126. | CrossRef
  127. | PubMed
  128. | Scopus (188)
  129. Lee na Nkeji edemede
  130. | CrossRef
  131. | PubMed
  132. | Scopus (41)
  133. Lee na Nkeji edemede
  134. | CrossRef
  135. | PubMed
  136. Lee na Nkeji edemede
  137. | CrossRef
  138. | PubMed
  139. | Scopus (3)
  140. Lee na Nkeji edemede
  141. | CrossRef
  142. | PubMed
  143. | Scopus (187)
  144. Lee na Nkeji edemede
  145. | nkịtị
  146. | Ederede zuru ezu
  147. | PDF zuru ezu
  148. | PubMed
  149. | Scopus (80)
  150. Lee na Nkeji edemede
  151. | CrossRef
  152. | PubMed
  153. | Scopus (522)
  154. Lee na Nkeji edemede
  155. Lee na Nkeji edemede
  156. | CrossRef
  157. | PubMed
  158. | Scopus (80)
  159. Lee na Nkeji edemede
  160. | CrossRef
  161. | PubMed
  162. | Scopus (1293)
  163. Lee na Nkeji edemede
  164. | CrossRef
  165. | PubMed
  166. | Scopus (777)
  167. Lee na Nkeji edemede
  168. | CrossRef
  169. | PubMed
  170. | Scopus (497)
  171. Lee na Nkeji edemede
  172. | CrossRef
  173. | PubMed
  174. Lee na Nkeji edemede
  175. | CrossRef
  176. | PubMed
  177. | Scopus (25)
  178. Lee na Nkeji edemede
  179. | CrossRef
  180. | PubMed
  181. | Scopus (32)
  182. Lee na Nkeji edemede
  183. | CrossRef
  184. | PubMed
  185. | Scopus (172)
  186. Lee na Nkeji edemede
  187. | CrossRef
  188. | PubMed
  189. | Scopus (93)
  190. Lee na Nkeji edemede
  191. | CrossRef
  192. | PubMed
  193. | Scopus (42)
  194. Lee na Nkeji edemede
  195. | nkịtị
  196. | Ederede zuru ezu
  197. | PDF zuru ezu
  198. | PubMed
  199. | Scopus (150)
  200. Lee na Nkeji edemede
  201. | PubMed
  202. Lee na Nkeji edemede
  203. | CrossRef
  204. | PubMed
  205. Lee na Nkeji edemede
  206. | CrossRef
  207. | PubMed
  208. Lee na Nkeji edemede
  209. | CrossRef
  210. | PubMed
  211. | Scopus (280)
  212. Lee na Nkeji edemede
  213. | CrossRef
  214. | PubMed
  215. | Scopus (12)
  216. Lee na Nkeji edemede
  217. | PubMed
  218. Lee na Nkeji edemede
  219. | CrossRef
  220. | PubMed
  221. | Scopus (1727)
  222. Lee na Nkeji edemede
  223. | CrossRef
  224. | PubMed
  225. | Scopus (5)
  226. Lee na Nkeji edemede
  227. | CrossRef
  228. | PubMed
  229. Lee na Nkeji edemede
  230. | CrossRef
  231. | PubMed
  232. | Scopus (605)
  233. Lee na Nkeji edemede
  234. | PubMed
  235. Lee na Nkeji edemede
  236. | CrossRef
  237. | PubMed
  238. | Scopus (3491)
  239. Lee na Nkeji edemede
  240. | CrossRef
  241. | PubMed
  242. | Scopus (78)
  243. Lee na Nkeji edemede
  244. | CrossRef
  245. | PubMed
  246. | Scopus (665)
  247. Lee na Nkeji edemede
  248. | CrossRef
  249. | PubMed
  250. | Scopus (90)
  251. Lee na Nkeji edemede
  252. | CrossRef
  253. | PubMed
  254. | Scopus (120)
  255. Lee na Nkeji edemede
  256. | CrossRef
  257. | PubMed
  258. | Scopus (7)
  259. Lee na Nkeji edemede
  260. | CrossRef
  261. | PubMed
  262. | Scopus (10)
  263. Lee na Nkeji edemede
  264. | CrossRef
  265. | PubMed
  266. | Scopus (77)
  267. Lee na Nkeji edemede
  268. | CrossRef
  269. | PubMed
  270. | Scopus (262)
  271. Sinha, R., Catapano, D., na O'Malley, S. Ọchịchọ nrụgide na nrụgide na-akpata nrụgide na ndị ọrụ cocaine. Psychopharmacology (Berl). 1999; 142: 343 – 351
  272. Sinha, R., Fuse, T., Aubin, LR, na O'Malley, SS Nchekasị nke uche, ihe metụtara ọgwụ na agụụ cocaine. Psychopharmacology (Berl). 2000; 152: 140 – 148
  273. Sinha, R., Talih, M., Malison, R., Cooney, N., Anderson, GM, na Kreek, MJ Hypothalamic-pituitary-adrenal axis na sympatho-adreno-medullary na-aza n’oge nrụgide nrụpụta na ọgwụ cueine na-akpata. Psychopharmacology (Berl). 2003; 170: 62 – 72
  274. Robbins, SJ, Ehrman, RN, ressmụ nwanyị, AR, Cornish, JW, na O'Brien, CP Ọnọdụ coodine na ojiji cocaine adịbeghị anya ejikọtara ya na ọkwa nke cocaine cue reactivity. Mmanya na-aba n’anya. 2000; 59: 33 – 42
  275. Koob, GF na Le Moal, M. Ise igbo na ụtaba na ụbụrụ na - egbochi ihe ụbụrụ Annu Rev Psychol. 2008; 59: 29 – 53
  276. Mantsch, JR, Vranjkovic, O., Twining, RC, Gasser, PJ, McReynolds, JR, na Blacktop, JM Usoro neurobiological nke na-enyere aka na cocaine metụtara nchegbu. Neuropharmacology. 2014; 76: 383 – 394
  277. Baker, TB, Piper, ME, McCarthy, DE, Majeskie, MR, na Fiore, MC Ihe na-akpali akpali riri ahụ: :dị nhazi nhazi na-emetụta ihe na-akwado adịghị ike. Psychol Rev. 2004; 111: 33 – 51
  278. Fox, HC, Hong, KI, Siedlarz, K., na Sinha, R. Enwela mmetụaka nke nrụgide na ọgwụ / mmanya na-agụsi mmadụ ike ịcaụ cocaine ma e jiri ya tụnyere ndị na-a socialụ mmanya. Neuropsychopharmacology. 2008; 33: 796 – 805
  279. Wheeler, RA, Twining, RC, Jones, JL, Slater, JM, Grigson, PS, na Carelli, RM Omume na njiri mara elektrik na-adịghị mma na-ebu amụma njikwa onwe nke cocaine. Neuron. 2008; 57: 774 – 785
  280. Cabib, S. na Puglisi-Allegra, S. Mesoaccumbens dopamine iji nagide nrụgide. Neurosci Biobehav Rev. 2012; 36: 79 – 89
  281. McCutcheon, JE, Ebner, SR, Loriaux, AL, na Roitman, MF Encododion nke mkpochapu site na dopamine na nucleus accumbens. N'ihu Neurosci. 2012; 6: 137
  282. Mirenowicz, J. na Schultz, W. Nrụsi ọrụ nke anụ ahụ dopamine neurons site na agụụ kama ịmasị mkpali. Nature. 1996; 379: 449 – 451
  283. Enweghị ike, MA, Magill, PJ, na Bolam, JP Na mgbochi nke dopamine neurons na mpaghara ventral tegmental mpaghara site na mkpali na-akpali akpali. Sayensị. 2004; 303: 2040 – 2042
  284. Roitman, MF, Wheeler, RA, Wightman, RM, na Carelli, RM Azịza kemịkal oge na-agba na akwara dị iche iche na-akwụghachi ụgwọ ma na-akpali akpali. Nat Neurosci. 2008; 11: 1376 – 1377
  285. Oleson, EB, Gentry, RN, Chioma, VC, na Cheer, JF Mwepu dopamine nke sekọndrị n’ime nje akwara na-ekwupụta ntaramahụhụ dị na ya na ihe ịga nke ọma ya. J Neurosci. 2012; 32: 14804 – 14808
  286. Badrinarayan, A., Wescott, SA, Vander Weele, CM, Saunders, BT, Couturier, BE, Maren, S., na Aragona, BJ Ihe na-akpali akpali ịgbanwoghari nke ọma na-agbasa ikike nnyonye anya dopamine n'ime akwara na -akpata isi na shei. J Neurosci. 2012; 32: 15779 – 15790
  287. Wheeler, RA, Aragona, BJ, Fuhrmann, KA, Jones, JL, Day, JJ, Cacciapaglia, F. et al. Udi cocaine n'eche ime ka ihe ndi ozo dabere na nhazi ugwo na onodu nke obi. Biol Psychiatry. 2011; 69: 1067 – 1074
  288. Beckstead, MJ, Gantz, SC, Ford, CP, Stenzel-Poore, MP, Phillips, PE, Mark, GP, na Williams, JT Nkwalite CRF nke ntanetị mgbasa ozi GIRK na dopamine neurons. Neuropsychopharmacology. 2009; 34: 1926 – 1935
  289. Wanat, MJ, Bonci, A., na Phillips, PE CRF na-eme ihe dị na etiti iji nwetaghachi mkpopụta dopamine iji nweta ụgwọ ọrụ mana ọ bụghị ndị buru ha amụma. Nat Neurosci. 2013; 16: 383 – 385
  290. Brischoux, F., Chakraborty, S., Brierley, DI, na Ungless, MA Phasic excitation nke dopamine neurons na ventral VTA site na mkpali na-enweghị isi. Proc Natl Acad Sci US A. 2009; 106: 4894 – 4899
  291. Matsumoto, M. na Hikosaka, O. Twodị abụọ nke dopamine neuron na-ekwupụta n'ụzọ doro anya mgbaàmà mkpali dị mma na nke na-adịghị mma. Nature. 2009; 459: 837 – 841
  292. Anstrom, KK, Miczek, KA, na Budygin, EA Pbawanye usoro nke dopamine phasic na ụzọ mesolimbic n'oge mmerụ mmekọrịta ọ bụla na oke. Neuroscience. 2009; 161: 3 – 12
  293. Wanat, MJ, Hopf, FW, Stuber, GD, Phillips, PE, na Bonci, A. Corticotropin na-ewepụta ihe na-eme ka mmelite mpaghara azụ ventral tegmental mpaghara dopamine neuron na-agbasi ike site na nkwalite protein na-adabere na protein Iase. J Physiol. 2008; 586: 2157 – 2170
  294. Bromberg-Martin, ES, Matsumoto, M., na Hikosaka, O. Dopamine na njikwa mkpali: inggwọ ,gwọ, ịghagharị, na ịmụrụ anya. Neuron. 2010; 68: 815 – 834
  295. Danjo, T., Yoshimi, K., Funabiki, K., Yawata, S., na Nakanishi, S. Omume na-emetụta mmụọ nke sitere na optogenetic inactivation nke mpaghara mpaghara dopamine neurons bụ onye na-anabata dopamine D2 na-anabata ụdọ akwara. Proc Natl Acad Sci US A. 2014; 111: 6455 – 6460
  296. Aragona, BJ, Liu, Y., Yu, YJ, Curtis, JT, Detwiler, JM, Insel, TR, na Wang, Z. Nucleus accumbens dopamine dị iche iche na-ekwu maka nguzobe na mmezi nke njikọ nwoke na nwanyị otu nwanyị. Nat Neurosci. 2006; 9: 133 – 139
  297. Ferguson, SM, Eskenazi, D., Ishikawa, M., Wanat, MJ, Phillips, PE, Dong, Y. et al. Hibzọ mgbochi mkpụrụ obi dị nwa oge na-ekpughe ọrụ ndị na-emegide ụzọ dị mfe na nke ụzọ ziri ezi na nghọta. Nat Neurosci. 2011; 14: 22 – 24
  298. Lobo, MK, Covington, HE 3rd, Chaudhury, D., Friedman, AK, Sun, H., Damez-Werno, D. et al. Lossdị sel nke akọwapụtara nke BDNF na-egosi mimics optogenetic nke ụgwọ ọrụ cocaine. Sayensị. 2010; 330: 385 – 390
  299. Lobo, MK na Nestler, EJ Esemokwu esemokwu na ọgwụ riri ahụ: Ọrụ dị iche na ụzọ agbachapụ agbatị obere akpa neurons. Neuroanat n'ihu. 2011; 5: 41
  300. Onwe, DW na Stein, L. Receptor subtypes dị na opioid na ụgwọ ọrụ mkpali. Pharmacol Toxicol. 1992; 70: 87 – 94
  301. Porter-Stransky, KA, Seiler, JL, Day, JJ, na Aragona, BJ Mmepe nke omume omume maka nhọrọ kachasị mma na-esochi nkwụghachi ụgwọ ọrụ a na-atụghị anya ya bụ mgbagha site na mbenata ụda D2-like receptor tone in the nucleus accumbens. Eur J Neurosci. 2013; 38: 2572 – 2588
  302. Richfield, EK, Penney, JB, na Young, AB Ntụnyere mmekọrịta nke anatomical na mmekọrịta n'etiti dopamine D1 na ndị na-anabata D2 na oke sistemụ oke. Neuroscience. 1989; 30: 767 – 777
  303. Stuber, GD, Wightman, RM, na Carelli, RM Mwepu nke nchịkwa onwe nke cocaine na-ekpughe arụmọrụ dopaminergic dị iche iche na nwa oge na ngụkọta akwara. Neuron. 2005; 46: 661 – 669
  304. Grill, HJ na Norgren, R. Ule reactivity ule. I. Mmeghachi nke mmụọ nke anụ ọkụkụ na - adịkarịsịrị n'ahụ. Resbụrụ Res. 1978; 143: 263 – 279
  305. Swanson, LW Brain Maps. Nke atọ ed. Elsevier Academic Press, Oxford, UK; 3
  306. Aragona, BJ, Cleaveland, NA, Stuber, GD, Day, JJ, Carelli, RM, na Wightman, RM Nkwalite kachasị nke nnyefe dopamine n'ime akwara nke na-eme ka ọnya ụdọ pụta site na cocaine bụ mmụba na mmeghe ntọhapụ nke phasic dopamine. J Neurosci. 2008; 28: 8821 – 8831
  307. Koob, GF na Le Moal, M. Iji ọgwụ ọjọọ eme ihe: Hysonic homeostatic dysregulation. Sayensị. 1997; 278: 52 – 58
  308. Shaham, Y., Shalev, U., Lu, L., De Wit, H., na Stewart, J. Ntughari usoro ịlaghachi ọgwụ: Akụkọ ihe mere eme, usoro na isi nchọta. Psychopharmacology (Berl). 2003; 168: 3 – 20
  309. Phillips, PE, Stuber, GD, Heien, ML, Wightman, RM, na Carelli, RM Mwepụta nke dopamine nke obere na-akwalite ịchọ cocaine. Nature. 2003; 422: 614 – 618
  310. Amamihe, RA Dopamine, mmụta na mkpali. Nat Rev Neurosci. 2004; 5: 483 – 494
  311. Blacktop, JM, Seubert, C., Baker, DA, Ferda, N., Lee, G., Graf, EN, na Mantsch, JR Akwụkwọ cocaine na-achọ ka ọ zaa maka nrụgide ma ọ bụ CRF nyefere na mpaghara ventral tegmental mpaghara na-esochi njikwa aka nke ogologo oge bụ nke onye na-anabata CRF 1 bụ onye mgbasa ozi CRF. J Neurosci. 2; 2011: 31 – 11396
  312. Hahn, J., Hopf, FW, na Bonci, A. Cocaine na -akpata na-akwalite corticotropin na-ewepụta ihe na-adabere na ike nke nnyefe nke ikuku na mpaghara dopamine neurons. J Neurosci. 2009; 29: 6535 – 6544
  313. Wang, B., Shaham, Y., Zitzman, D., Azari, S., Amamihe, RA, na Gị, ZB Ahụmahụ cocaine na-ewepụta nchịkwa nke glucose midbrain na dopamine site na ihe na - ahapụ ọrụ corticotropin: Ọrụ dị na ndọghachi azụ na - akpata nchekasị na ịchọ ọgwụ. J Neurosci. 2005; 25: 5389 – 5396
  314. Wang, B., Gị, ZB, Osikapa, KC, na Amamihe, RA Ntighaghagharia obi na acho acho acho: Ọrụ maka CRF (2) onye na enweta protein na CRF na-eke n’oghere uzo nke oke. Psychopharmacology (Berl). 2007; 193: 283 – 294
  315. Owesson-White, CA, Roitman, MF, Sombers, LA, Belle, AM, Keithley, RB, Peele, JL et al. Isi mmalite na-enye aka na mgbakwunye ndọtị dopamine na ngụkọta akwara. J Neurochem. 2012; 121: 252 – 262
  316. Na-enweghị mgbagha, MA, Singh, V., Crowder, TL, Yaka, R., Ron, D., na Bonci, A. Corticotropin na-ewepụta ihe chọrọ CRF na-ejikọ protein na ndị na-anabata NMDA na-anabata ihe site na CRF receptor 2 na neprons dopamine. Neuron. 2003; 39: 401 – 407
  317. Kalivas, PW na Duffy, P. Oge extracellular dopamine na ezi mmetụta na cocaine. I. Dopamine axon terminal. J Neurosci. 1993; 13: 266 – 275
  318. Thierry, AM, Tassin, JP, Blanc, G., na Glowinski, J. Nhọrọ nke usoro mesocortical DA site na nrụgide. Nature. 1976; 263: 242 – 244
  319. Abercrombie, ED, Keefe, KA, DiFrischia, DS, na Zigmond, MJ Mmetụta dịgasị iche iche nke nrụgide na ntọhapụ vivo dopamine na striatum, ngwongwo akwara, na etiti ihu ihu. J Neurochem. 1989; 52: 1655 – 1658
  320. McFarland, K., Davidge, SB, Lapish, CC, na Kalivas, PW Limbic na moto elele na - akpata mmeghachi nke mmekpa ahụ maka ịkpa ike. J Neurosci. 2004; 24: 1551 – 1560
  321. Hikida, T., Yawata, S., Yamaguchi, T., Danjo, T., Sasaoka, T., Wang, Y., na Nakanishi, S. Uzọ ngagharị bara ụba nke akụrụngwa na - erite ụgwọ ọrụ na akarị mkpesa site na ndị na - anabata ndị na - anabata ya. Proc Natl Acad Sci US A. 2013; 110: 342 – 347
  322. Smith-Roe, SL na Kelley, AE Ime ka ọnụnọ mkpụrụ nke NMDA na ndị na-anabata doxamine D1 n'ime akụrụngwa ngwongwo a chọrọ maka mmụta ngwa ọrụ. J Neurosci. 2000; 20: 7737 – 7742
  323. Berridge, KC na Robinson, TE Kedu ihe bụ dopamine na ụgwọ ọrụ: Mmetụta Hedonic, inwetụ ụgwọ ọrụ, ma ọ bụ iji ịnụ ọkụ ọkụ? Brain Res Brain Res Rev. 1998; 28: 309 – 369
  324. Onye maara ihe, RA na Koob, GF Mmepe na mmezi nke ọgwụ riri ahụ. Neuropsychopharmacology. 2014; 39: 254 – 262
  325. Solomon, RL na Corbit, JD Usoro usoro mmegide na-akpali. II. Ise siga. J Abnorm Psychol. 1973; 81: 158 – 171
  326. Solomon, RL na Corbit, JD Usoro usoro mmegide na-akpali. I. Ọnọdụ nwa oge nke emetụta. Psychol Rev. 1974; 81: 119 – 145
  327. Wikler, A. Ọganihu na-adịbeghị anya na nyocha banyere ntọala neurophysiologic nke ọgwụ riri ahụ. Am J psychiatry. 1948; 105: 329 – 338
  328. Robinson, TE na Berridge, KC Ntọala ndabere nke agụụ ọgwụ: Ozizi riri ahụ na-akpali akpali. Brain Res Brain Res Rev. 1993; 18: 247 – 291
  329. Stewart, J. Mmetụta ọgwụ nọrọ n'ọnọdụ na enweghị nchịkwa na nlọghachi azụ na ọgwụ nchịkwa onwe. Prog Neuropsychopharmacol Biol Psychiatry. 1983; 7: 591 – 597
  330. Stewart, J., de Wit, H., na Eikelboom, R. Ọrụ nke ọgwụ mmetụta na-enweghị ọnọdụ na ọnọdụ oyi na njikwa onwe onye nke opiates na mkpali. Psychol Rev. 1984; 91: 251 – 268
  331. Stewart, J. na onye maara ihe, RA Mweghachi nke omume nchịkwa onwe onye nke heroin: Morphine kpaliri na naltrexone na-akụda mmụọ ịmaliteghachi mmeghachi omume mgbe ikpochasị ya. Psychopharmacology (Berl). 1992; 108: 79 – 84
  332. Kenny, PJ, Chen, SA, Kitamura, O., Markou, A., na Koob, GF Ọnọdụ iwere afọ nwere na-eme ka ike ọgwụ heroin kwụsịlata ma na-ebelata ụgwọ ọrụ. J Neurosci. 2006; 26: 5894 – 5900
  333. Willuhn, I., Burgeno, LM, Groblewski, PA, na Phillips, PE Co coụ ọgwụ cocaine riri oke na-esite n'ọkụ iji dolata nke ọma dopamine. Nat Neurosci. 2014; 17: 704 – 709
  334. Koob, GF Nkwalite na-adịghị mma na ọgwụ riri ahụ: ọchịchịrị dị n'ime. Opr Neurobiol Curr. 2013; 23: 559 – 563
  335. Tsibulsky, VL na Norman, AB Atizọ Satiety: Ihe atụ buru ibu nke njikwa onwe onwe cocaine. Resbụrụ Res. 1999; 839: 85 – 93
  336. Onye maara ihe, RA, Newton, P., Leeb, K., Burnette, B., Pocock, D., na ikpe ziri ezi, JB Jr. Mgbanwe dị na akwara na-agbakọta ịta ahụhụ dopamine n'oge nchịkwa onwe ịgwọ onwe cocaine na oke. Psychopharmacology (Berl). 1995; 120: 10 – 20