COMMENTS: Delta FosB shine ɗayan ƙwayoyin farko na jaraba. Yana tashi, ko tarawa, yayin aiwatar da jaraba, ƙarfafa halayyar jaraba da sake sake kwakwalwa. Yana tashi ko jarabawar ta sinadarai ce ko ta ɗabi'a. Wannan binciken ya nuna cewa yana taruwa yayin jima'i da shan sukari. Masu binciken sun kuma gano cewa yin jima’i ya kara yawan amfani da sikari. Delta FosB na iya kasancewa cikin jaraba ɗaya yana ƙarfafa wani buri. Tambayar ita ce - ta yaya “yawan cin” batsa yake shafar Delta FosB? Tunda yana da dopamine wanda yake farawa a DeltaFosB, duk ya dogara da kwakwalwar ku.
Nazarin cikakken: Rashin Halin ΔFosB a cikin Al'adu Accumbens akan Ra'ayin Halittar Abubuwan Hulɗa
J Neurosci. 2008 Oktoba 8; 28 (41): 10272–10277. Doi: 10.1523 / JNEUROSCI.1531-08.2008.
Deanna L Wallace1,2, Vincent Vialou1,2, Loretta Rios1,2, Tiffany L. Carle-Florence1,2, Sumana Chakravarty1,2, Arvind Kumar1,2, Danielle L. Graham1,2, Thomas A. Green1,2, Anne Kirk1,2, Sergio D. Iñiguez3, Linda I. Perrotti1,2,4, Michel Barrot1,2,5, Ralph J. DiLeone1,2,6, Eric J. Nestler1,2, da kuma Carlos A. Bolaños-Guzmán1,2,3 +
+ Bayanan marubucin
Adireshin DL Wallace na yanzu: Helen Willis Neuroscience Institute, Jami'ar California, Berkeley, Berkeley, CA 94720.
Adireshin TL Carle-Florence na yanzu: Laboratories na bincike na Mary Kay, Dallas, TX 75379.
Adireshin DL Graham na yanzu: Merck Laboratories, Boston, MA 02115.
TA Green adireshin yanzu: Virginia Commonwealth University, Richmond, VA 23284.
Adireshin EJ Nestler na yanzu: Ma'aikatar Neuroscience, Dutsen Sinai School of Medicine, New York, NY 10029.
Abstract
Sakamakon sakonnin deltaFosB (ΔFosB), wanda aka haifar a cikin mahaifa accumbens (NAc) ta hanyar daukan hoto ga magungunan ƙwayoyi, an nuna shi don magance wadannan magunguna. Duk da haka, ƙananan an san game da rawar da ake yi na ΔFosB a cikin gyaran martani ga sakamakon lada. A nan, muna nuna cewa dabi'u biyu na dabi'u na dabi'a, maye gurbi da halayyar jima'i, ƙara yawan ΔFosB a cikin NAc. Daga nan sai muyi amfani da hanyar canzawa ta hanyar bidiyo mai hoto don nazarin yadda irin wannan ΔFosB ya haifar da amsoshin halayen waɗannan sakamako. Muna nuna cewa rashin fahimta na ΔFosB a cikin NAC yana kara yawan ciwon sukari da kuma bunkasa hali na jima'i. Bugu da ƙari kuma, muna nuna cewa dabbobin da ke da jima'i na yau da kullum, wanda ya nuna yawan karuwar ΔFosB, kuma ya nuna yawan karuwar amfani da sucrose. Wannan aikin ya nuna cewa ΔFosB ba wai kawai an jawo shi ba a cikin NAC ta hanyar maganin zalunci, amma ta hanyar ladabi mai mahimmanci. Bugu da ƙari, bincikenmu ya nuna cewa yawancin abin da ke faruwa a cikin kwakwalwar da ke haifar da ΔFosB a cikin NAc zai iya ƙara amfani da sauran ladaran lada.
Gabatarwa
ΔFosB, asali na Fos iyali, shi ne samfurin ƙaddamarwa na fosB gene (Nakabeppu da Nathans, 1991). An bayyana shi a ƙananan ƙananan matakai idan aka kwatanta da sauran furotin na iyali na Fos don amsawa ga matsalolin da ke cikin kwakwalwa, amma ya karu zuwa ƙananan matakai a kwakwalwa bayan ƙarfafawa ta yau da kullum saboda yanayin da ya dace (ganin Nestler, 2008). Wannan kamfani yana faruwa ne a cikin wani yanki na musamman don amsa yawan nau'o'in ci gaba na yau da kullum, ciki har da ci gaba da maganin magungunan maganin, cin zarafi, maganin antidepressant, kwayoyin cutar antipsychotic, raunuka neuronal, da kuma irin nauyin danniya (don dubawa, gani Cenci, 2002; Nestler, 2008).
Hakanan sakamakon aikin ΔFosB shine mafi kyau ga magungunan zalunci, wanda ya haifar da sunadaran mafi girma a cikin ƙwayar mahaifa (NAc), wani rahoto ya ruwaito kusan dukkanin magungunan magunguna (duba McDaid et al., 2006; Muller da Unterwald, 2005; Nestler, 2008; Perrotti et al., 2008). NAC na cikin ɓangare na ventral striatum kuma yana da mahimmancin matakan neural don ayyukan da ake amfani da su na cin zarafi. Saboda haka, karin shaida yana nuna cewa shigarwa ta ΔFosB a wannan yanki na ƙaruwa da hankali ga dabba a sakamakon sakamakon lalacewar magungunan ƙwayoyi kuma yana iya kara haɓaka don samun su. Sabili da haka, bayyanar da ΔFosB a cikin NAC na sa dabbobi su ci gaba da zama wurin da za a zabi cocaine ko zuwa morphine, ko kuma yin maganin cocaine, a ƙananan maganin miyagun ƙwayoyi, da kuma inganta ƙwanƙwasawa don maganin cocaine a cikin tsari mai ci gaba (Colby et al., 2003; Kelz et al., 1999; Zachariou et al., 2006).
Bugu da ƙari, da rawar da ya taka wajen magance magungunan miyagun ƙwayoyi, NAC ya kasance cikin rikodin mayar da martani ga sakamakon ladabi, kuma aikin kwanan nan ya ba da shawarar dangantaka tsakanin ladabi da kuma ΔFosB. An nuna motsi na motsawa don ƙara yawan ΔFosB a cikin NAc, da kuma nuna rashin jin dadi na ΔFosB a cikin wannan kwakwalwar kwakwalwa yana haifar da karuwar cigaba da ke gudana na tsawon makonni idan aka kwatanta da kula da dabbobin da ke cikin kwarya a cikin makonni biyu (Werme et al., 2002). Hakazalika, cin abinci mai yawan gaske ya jawo ΔFosB a cikin NAc (Teegarden da Bale, 2007), yayin da ΔFosB overexpression a wannan yankin yana ƙarfafa kayan aiki don amsawa ga sakamako na abinci (Olausson et al., 2006). Bugu da ƙari, da fosB Ra'ayin da aka haifa a cikin halayyar mahaifiyar (Brown et al., 1996). Duk da haka, ƙananan bayanai suna samuwa a kan dangantaka tsakanin ΔFosB da halayen jima'i, daya daga cikin sakamako mafi girma. Bugu da ƙari, ƙananan bayyana har yanzu yana da yiwuwar shigar da ΔFosB a cikin mafi mahimmanci, har ma da "jaraba", nau'i na yanayin halin ladabi. Alal misali, da dama rahotanni sun nuna wani batu-kamar bangare a cikin tsarin sa maye gurbi (Avena et al., 2008).
Don yada iliminmu game da aikin ΔFosB a cikin halin halayen dabi'a, mun bincika yadda aka shigar da ΔFosB a cikin NAC a cikin shaye-shaye da halayyar jima'i. Mun kuma ƙaddara yadda yawancin ΔFosB a cikin NAC ya sauya halayen halayen halayen waɗannan ladabi, kuma idan har yanzu ya nunawa wani sakamako na halitta zai iya bunkasa sauran dabi'u mai ladabi.
Kaya da matakai
Dukkan hanyoyin dabba da aka yarda da su ta hanyar Hukumar kulawa da jinin dabbobi da UT ta Kudu ta kudu.
Halin jima'i
An haifi dan uwan Sprague-Dawley a cikin jima'i (Charles River, Houston, TX) ta hanyar barin su su kasance tare da mata masu karɓa har zuwa haɗuwa, kamar 1-2 sau daya a kowane mako don 8-10 makonni don jimlar 14. An yi la'akari da halin jima'i kamar yadda aka bayyana (Barrot et al., 2005). Mazauna maza suna samuwa ta hanyar ɗaukar hotuna zuwa wannan fagen fama da kwanciya, domin yawancin lokaci, kamar yadda mazajen da aka sani. Ba a taɓa gabatar da mata a cikin gidan wasan ba tare da waɗannan mazajen. A gwaje-gwaje na daban, an kafa wani ƙarin gwajin gwagwarmaya: an gabatar da maza zuwa mace mai kula da cutar hormone wanda bai riga ya shiga bace. Wadannan maza sunyi ƙoƙari su shiga matsugunni, duk da haka tun da mata ba su karba ba, ba a samu halayyar jima'i ba a wannan rukuni. Kwana goma sha takwas bayan zaman karshe, an yi amfani da dabbobin da ba su da kullun kuma sunyi amfani da kwakwalwa don aiki. Ga wani rukuni na dabbobi, kamar kimanin 5 bayan 14th zaman, an gwada zabar sucrose kamar yadda aka bayyana a kasa. Duba Hanyar Ƙarin domin karin bayani.
Sucrose amfani
A cikin gwaji na farko (Hoto 1A), an ba da ratsi zuwa ga kwalabe biyu na ruwa ga 2 kwanakin, sai kwalba ɗaya ya bi kowace ruwa da sucrose don 2 kwanakin a kowane ƙananan ƙwayar sucrose (0.125 zuwa 50%). Awanin 6 na kwalabe na ruwa guda biyu kawai suka bi, bayan kwana biyu na kwalban ruwa daya da kwalban 0.125% sucrose. A gwaji na biyu (Hoto 1b-c, Figure 2), an ba ratsi damar samun damar shiga kowane kwalban kowane ruwa da 10% sucrose don 10 kwanakin. Gudanar da dabbobi sun karbi kwalabe biyu na ruwa kawai. An yi amfani da dabbobi da sauri ko kuma sunyi kwakwalwa kuma an tattara kwakwalwa don aiki.
Kwafin zabi guda biyu
An gudanar da tsari mai nau'i biyu na kwalba kamar yadda aka bayyana a baya (Barrot et al., 2002). Kafin aikin tiyata, don sarrafawa don yiwuwar bambance-bambancen mutum, an gwada dabbobi a lokacin 30 min na farko na lokacin duhu don yin amfani da zabi biyu a tsakanin ruwa da 1% sucrose. Makonni uku bayan karɓan jigilar kwayoyin halitta (duba ƙasa) da kuma kafin wani gwaji na halin kirki, an ba dabbobi kyauta kawai ruwa don hanyar zabin 30-min a madadin ruwa da 1% sucrose bayani.
Dabbobi masu kula da jima'i da kula da dabbobi ba su da hanyar gwaji kafin yin jima'i. Bayan kwana biyar bayan zaman 14th na halin jima'i (ko iko), an ba da dabbobi jigilar gwaji guda biyu tsakanin ruwa da wani bayani na 1% sucrose a lokacin 30 min na farko na fadin haske. An rarraba bangarori daban-daban na dabbobi masu jima'i da kulawa don yin la'akari da matakan ΔFosB bayan halayyar jima'i da kuma nazarin tasiri akan halayen jima'i a kan zabar sukayi.
Western Blotting
An rarraba fassarar NAc da aka samu ta hanyar rarraba fassarar ta hanyar Yammacin Turai kamar yadda aka bayyana a baya (Perrotti et al., 2004), ta yin amfani da antitos polyclonal anti-FosB antibody (duba Perrotti et al., 2004 don nuna bambancin satar jikin mutum) da kuma wani wanda ya sanya kwayar cutar guda daya zuwa glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (RDI-TRK5G4-6C5; Diagnostics Research, Concord, MA, USA), wanda ya kasance mai gina jiki. ΔFosB sunadaran sunadaran sunadarai ga GAPDH, da gwaji da kuma sarrafa samfurori idan aka kwatanta su. Duba Hanyar Ƙarin domin karin bayani.
Immunohistochemistry
Ana amfani da dabbobi da kwakwalwa ta hanyar kwakwalwa ta hanyar amfani da hanyoyin immunohistochemistry da aka wallafa (Perrotti et al., 2005). Tun lokacin da aka shafe kwanaki masu zuwa a sakamakon 18-24 kafin a yi nazari, mun dauki dukkanin FosB-kamar ƙananan cuta, wanda aka gano tare da wani FosB antibody (SC-48, Santa Cruz Biotechnology, Santa Cruz, CA, Amurka), don yin tunãni ΔFosB (Perrotti et al., 2004, 2005). Duba Hanyar Ƙarin domin karin bayani.
Kwayar Viral-Mediated Gene Canja wurin
An yi tiyata a kan ratsan namiji Sprague-Dawley. An kwantar da kwayoyin cutar ta Adeno (AAV), watau 1.5 μl a gefe, cikin NAc kamar yadda aka bayyana a baya (Barrot et al., 2005). An tabbatar da wuri mai kyau bayan gwaje-gwaje a kan sassan layi na 40 μm cresyl-violet. Vectors sun haɗa da wani iko da ke nuna furotin gine-gine mai sauƙi (GFP) (AAV-GFP) ko AAV na bayyana nau'in iri-iri na ΔFosB da GFP (AAV-ΔFosB) (Zachariou et al., 2006). Bisa ga lokacin lokaci na magana a cikin NAc, an gwada dabbobi don halartar 3-4 makonni bayan an yi amfani da su na AAV vectors, lokacin da fadin transgene ya fi girma (Zachariou et al., 2006). Duba Hanyar Ƙarin domin karin bayani.
Nazarin lissafi
An auna mahimmancin mahimmanci ta amfani da ma'auni maimaita abubuwa guda biyu ANOVAs da kuma gwajin ɗalibi, waɗanda aka gyara inda aka lura da kwatancen da yawa. Ana bayyana bayanai azaman ± SEM. An bayyana mahimman ilimin lissafi azaman * p <0.05.
results
Gwanin lokaci mai yaduwa zuwa sucrose yana haifar da karuwar cigaban sukari da kuma dabi'arsu
Mun aiwatar da wani nau'in nau'i na zabi guda biyu wanda aka sanya nauyin haɗin sukari kamar ninki biyu a cikin kwana biyu bayan 2 kwanakin kwalabe na ruwa guda biyu. Sakamakon da aka yi da sukari ya fara a 0.125% kuma ya karu zuwa 50%. Dabbobi ba su nuna nuna sha'awar sucrose ba sai 0.25% sucrose, sannan kuma ya sha ruwa fiye da ruwa a kowane taro mai girma. Farawa a cikin 0.25% maida hankali, dabbobi suna shan yawan sukarin sukarin har sai an sami nauyin ƙarar yarinya a 5 da 10%. A 20% da kuma mafi girma, sun fara rage yawan sukarin suro don su ci gaba da kasancewa a cikin jiki na sukari (Hoto 1A da kuma saiti). Bayan wannan yanayin, dabbobin sun ciyar da 6 kwanaki biyu tare da kwalabe na ruwa guda kawai, sannan aka gabatar da zabi 0.125% sucrose ko ruwa na kwana biyu. Dabbobi sun sha ruwa fiye da ruwa a wannan taro, kuma sun nuna fifiko mai kyau na likitanci idan aka kwatanta da rashin fifiko da aka gani a lokacin da aka fara nunawa ga wannan saiti a cikin ranar 1.
Saboda an kai gagarumin karfin girma a wani taro na 10%, an ba da tsuntsaye masu haɓaka tsakanin wata kwalban ruwa da kwalban 10% sucrose don kwanakin 10 kuma idan aka kwatanta da ƙungiyar kulawa da aka bai wa kwalabe biyu na ruwa kawai. Dabbobi masu ciwon sukari sun gina matakan da sukayi amfani da su a cikin rana 10 (Hoto 1b). Har ila yau, sun sami karuwar nauyin da suka fi dacewa bayan an cigaba da yaduwar sukari yayin da aka kwatanta da kula da dabbobi, tare da bambancin nauyi a kan lokaci (Hoto 1c).
Ruwan ƙwayar cuta yana ƙara yawan ΔFosB a cikin NAc
Mun bincika wadannan dabbobin a kan tsarin 10% sucrose na matakan ΔFosB a cikin NAc ta hanyar yin amfani da Tsarin Yamma (Hoto 2A) da kuma immunohistochemistry (Hoto 2b). Duk hanyoyi guda biyu da aka saukar da shigar da sunadarin ΔFosB a cikin wannan kwakwalwa a yankin da aka samu idan aka kwatanta da kula da dabbobi. Tun da dukan jerin ƴan furotin na ΔFosB sun ƙunshi cikin wannan FosB cikakke, ƙwayoyi masu amfani da su don gane FosB-kamar immunoreactivity gane duka sunadaran (Perrotti et al., 2004, 2005). Duk da haka, Yunkuri na yamma ya nuna cewa kawai ΔFosB ne mai rinjaye ta hanyar sucrose-shan. Wannan yana nuna bambanci a sigina da aka gano ta hanyar immunohistochemistry wakiltar ΔFosB. An karu da karuwa a Hoto 2b aka samo a cikin NAC da kuma harsashi, amma ba dorsal striatum (ba a nuna ba).
Harkokin jima'i yana ƙaruwa a matakin NAC
Mun sake bincika sakamakon ciwon halayen jima'i a kan shigar da ΔFosB a cikin NAc. An yi amfani da ratsan jinsi masu jima'i don samun damar samun dama tare da mace mai karɓa har zuwa haɗin 14 a kan wani lokaci na 8-10. Abu mai mahimmanci, dabbobi masu kula da dabbobi ba su da iko a gida, amma a maimakon haka an samo su ta hanyar daidaitawa a kan gwaji da kuma nunawa a fagen filin wasa da kuma kwanciya wanda yayinda katako ya faru akan lokaci ɗaya amma ba tare da nunawa ga mace mai karɓa ba, sarrafawa ga haɓakawa da maganganu. Yin amfani da ƙuƙwalwar Yamma, mun gano cewa ilimin jima'i yana ƙaruwa sosai na ΔFosB idan aka kwatanta da ƙungiyar kulawa (Hoto 2A), ba tare da wani matakan da aka gano na FosB cikakke ba. Dangane da waɗannan bayanan, immunohistochemistry ya nuna yawan karuwar ΔFosB a tsakiya da harsashi na NAc (Hoto 2c), amma ba dorsal striatum (ba a nuna) ba.
Don tabbatar da cewa karuwa a ΔFosB da aka lura a cikin dabbobin da aka samu a cikin jima'i ba saboda haɗin kai ba ne ko wasu abubuwan da ba su da alaka da juna ba, muna samar da namiji marar jima'i wanda aka nuna wa mata da aka kula dasu, amma ba a yarda su yi koyi ba. Wadannan maza ba su nuna bambanci a cikin matakan ΔFosB ba idan aka kwatanta da wani ɓangare na tsararraki-dabba da ke kulawa da dabbobi (Fig. 2A), suna nuna cewa shigarwa ta ΔFosB yana faruwa ne saboda mayar da hankali ga halayyar jima'i da ba zamantakewa ko maras amfani ba.
Sakamakon ΔFosB a cikin NAC yana ƙaruwa cike da sucrose
Yin amfani da tsarin maganin maganin rigakafi da bidiyo, wanda ya ba da damar barcin ΔFosB akan makonni da yawa (Zachariou et al., 2006) (Hoto 3A), mun bincika tasiri na matakan ΔFosB, musamman akan wannan NAC, a kan halayyar sa maye gurbi (Hoto 3b). Mun fara tabbatar da cewa babu bambance-bambance a cikin halayen sucrose na yau da kullun kafin a fara tiyata tare da gwajin gwaji na farko (AAV-GFP: 6.49 ± 0.879 ml; AAV-ΔFosB: 6.22 ± 0.621 ml, n = 15 / rukuni, p> 0.80 ). Makonni uku bayan aikin tiyata, lokacin da bayanin ΔFosB ya daidaita har tsawon kwanaki ~ 10, an ba dabbobi gwajin bayan aikin tiyata. Aungiyar AAV-ΔFosB ta sha mafi nasara fiye da ƙungiyar kulawa ta AAV-GFP (Hoto 3b). Babu bambanci a cikin yawan shan ruwa tsakanin kungiyoyin biyu (AAV-GFP: 0.92 ± 0.019 ml; AAV-ΔFosB: 0.95 ± 0.007 ml, n = 15 / rukuni, p> 0.15), yana mai nuna cewa tasirin ΔFosB ya ƙayyade ga sucrose.
Sakamakon ΔFosB a cikin NAC yana tasiri game da halayen jima'i
Na gaba, mun bincika ko bayyanar ΔFosB a cikin NAc yana tsara halayyar jima'i da na dabba da dabbobin da suka ji daɗi. Kodayake ba mu sami wata bambance-bambance a cikin sigogi na halayyar jima'i tsakanin AAV-ΔFosB da -GFP da aka shawo kan dabbobi (duba Ƙarin S1 Siffar), Sakamakon ΔFosB a cikin dabbobi masu haɗari ya rage yawan adadin abubuwan da ake bukata don isa ga haɓaka don halayen halin jima'i na farko (Hoto 3c). Har ila yau, akwai tasowa na ragewa a lokacin jinkirta ga kungiyar ΔFosB bayan bin jima'i na farko na jima'i. (Hoto 3c). Ya bambanta, babu bambancin da aka yi a cikin latencies don fitarwa, intromissions, ko musgunawa a cikin maciji ko dabbobin da suka ji daɗi (duba Ƙarin S1 Siffar). Hakazalika, babu wani bambanci da aka samu saboda ragowar intromission (yawan ƙwayar cuta / [yawan adadi mai yawa]], ko da yake wannan zai iya zama saboda yawancin haɓaka a yawan adadin kowane ɗayan.
Jima'i kwarewa ƙaruwa sucrose ci
Tun lokacin da muka sami karuwa a matakin NAV bayan da sukayi shan taba da kuma jima'i, kuma ΔFosB overexpression yana tasiri halayen hali na biyan biyun, yana da sha'awar gano ko kafin a nunawa daya daga cikin ladabi ya shafi tasirin hali ga ɗayan. Kafin sanin jima'i, an ba da dabbobi marasa kyau don sarrafawa ko yanayin jima'i. An bayyana dabbobin dabbobi ga abubuwan jima'i ko yanayin kulawa, kamar yadda aka bayyana a baya, a cikin makonni 8-10. Bayan kwana biyar bayan jima'i na jima'i, an hura dabbobi a 30-min nau'i nau'i biyu na zafin zabi tsakanin ɗayan kwalban ruwa da daya daga cikin sucrose. Mun gano cewa shafukan da aka samu a jima'i suna sha ruwan inabi fiye da ikos (Hoto 3b). Ba a bambanta tsakanin dabbobi da jima'i da dabbobi ba tare da amfani da ruwa (Manajan: 1.21 ± 0.142 ml; Jima'i Ganin: 1.16 ± 0.159 ml, n = 7-9, p = 0.79), yana nuna cewa sakamako yana da mahimmanci ga sucrose.
tattaunawa
Wannan binciken ya haɗu da wani ɓangaren da ya gabata a cikin wallafe-wallafe a cikin matsin lamba na ΔFosB a yanayin dabi'a na ladabi dangane da jima'i da sucrose. Mun fara tashi don sanin ko ΔFosB ya tara a cikin NAc, wani yanki na ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwar ajiya, bayan ɗaukar hoto mai yawa ga sakamakon ladabi. Wani muhimmin fasali na wannan aikin shine ba wa dabbobi damar zabi a cikin halin su, ta hanyar kwatanta yanayin da ake gudanarwa ta miyagun kwayoyi. Wannan shi ne tabbatar da cewa duk wani tasiri akan matakan ΔFosB ya danganci amfani da kyautar da aka samu. A tsarin sucrose (Figure 1) ya nuna irin nau'o'in jaraba-dabi'un da aka kwatanta da sauran samfurori da sukayi amfani da su: zabi a tsakanin sakamako da iko, hanyar mayar da martani na U-shaped, amsa bayanan bayan janyewa, da kuma amfani da kima. Tsamfurinsa yana haifar da karuwar samun karuwar, ba a gani ba a wasu nau'o'in kamar misalin sukari na yau da kullum (Avena et al., 2008).
Bayanan mu na kafa, a karon farko, cewa nau'i nau'i biyu na ladabi, lalacewa da jima'i, sun haɓaka matakan ΔFosB a cikin NAc. Wadannan haɓakawa sun lura da su na Yammacin Turai da immunohistochemistry; ta amfani da hanyoyi guda biyu na tabbatar da cewa samfurin abincin kiyayewa hakika ΔFosB kuma ba cikakke FosB ba, wani samfurin na fosB gene. Sakamakon zabe na ΔFosB ta hanyar sucrose da jima'i yana kama da zaɓin da aka zaba na ΔFosB a cikin NAc bayan gwaninta na kusan dukkanin magungunan magunguna (duba Gabatarwa). Amma bayanin kula, duk da haka, kallo ne cewa matakin ΔFosB shigarwa a cikin NAc da aka lura a nan don mayar da martani ga sakamakon ladabi ya fi karami idan aka kwatanta da abin da aka gani don maganin miyagun ƙwayoyi: maye gurbi da halayen jima'i ya haifar da karuwar 40-60% a matakan ΔFosB bambanta da sau da yawa shigarwa gani tare da kwayoyi masu yawa na zagi (Perrotti et al., 2008).
Hanya na biyu na wannan binciken shi ne bincika aikin aikin ΔFosB shigarwa a cikin NAc akan yanayin halayen dabi'a. Mafi yawan ayyukanmu na baya akan tasiri ΔFosB akan sakamako na miyagun ƙwayoyi ya yi amfani da ƙwayoyin mikiya bitransgenic, inda aka bayyana ΔFosB magana ga NAc da dorsal striatum. Wadannan ΔFosB masu launin miki suna nuna halayen halayyar halayyar halayyar hawan cocaine da haɓaka, da kuma karin motar da ke motsawa da kayan aiki don neman abinci (duba Gabatarwa). A cikin wannan binciken, mun yi amfani da tsarin canza hanyar canzawa ta hanyar kyakyawan kwayar cutar ta hanyar kwanan nan don tabbatar da tsarfin ΔFosB a cikin yankuna masu kwakwalwa na maza.Zachariou et al., 2006). Mun samo a nan cewa ΔFosB ta daɗaɗa hankali ya karu da ciwon sukari yayin da aka kwatanta da kula da dabbobi, ba tare da bambance-bambance a cikin ruwa a tsakanin kungiyoyi biyu ba.
Mun kuma bincika yadda ΔFosB ke shafar halayyar jima'i. Mun nuna cewa ΔFosB overexpression a cikin NAC ya rage yawan adreshin da ake buƙata don haɗuwa a cikin dabbobin da suka shafi jima'i. Wannan bai dace da wasu bambance-bambance a cikin halayen jima'i ba, ciki har da gyare-gyare a kan dutse, intromission, ko latencies. Bugu da ƙari, ΔFosB overexpression ba ta shafi wani ɓangare na halin jima'i a cikin dabbobin jin dadin jima'i. Rashin yin amfani da magudi a cikin NAC don tasiri da halayen jima'i ba abin mamaki bane saboda bada tabbacin cewa kwakwalwar wannan ladabi ta ba da lada ga yanki na al'adar (Balfour et al., 2004; Hull da Dominguez, 2007). Rashin karuwar ΔFosB da yawa a cikin ƙananan halayen zai iya nuna ingantaccen halayyar jima'i, a cikin wadannan dabbobi masu nuni da ΔFosB na nunawa a cikin NAc suna nuna kamar dabbobi masu kayanawa. Alal misali, a gwaje-gwajen gwagwarmaya ta jima'i, dabbobin suna buƙatar ƙananan haɗuwa su kai ga haɗuwa (Lumley da Hull, 1999). Bugu da ƙari, yanayin da ake samu na ragewa a lokacin jinkirin jinkiri (PEI) tare da ΔFosB overexpression yana nuna halin da ake gani a cikin wasu abubuwan da ke da sha'awa,Kippin da van der Kooy, 2003). TDukkanin waɗannan binciken sun nuna cewa ΔFosB Cunkushewa a cikin dabbobi masu rai na iya taimakawa wajen yin jima'i ta hanyar sanya dabbobi masu kama da kwarewa ko dabbobin jima'i. A gefe guda kuma, ba mu lura da wani muhimmin tasiri na ΔFosB ba game da halin jima'i. Ƙarin halayen halayyar halayyar halayyar jima'i (misali, wuri na musamman) zai iya nuna bambanci da sakamakon da ake samu na ΔFosB.
A ƙarshe, mun bincika yadda za a iya nunawa ga wani sakamako na halitta wanda ya shafi halayyar hali zuwa wani. Musamman, mun ƙaddara tasirin tasirin jima'i a kan maye gurbin. Kodayake magunguna biyu da dabbobin da suka shafi jima'i suna nuna kyakkyawan fata ga sucrose, Kwayoyin da suka shafi jima'i suna shan ruwan sha, ba tare da canza canjin ruwa ba. Wannan bincike ne mai ban sha'awa, a cewa yana nuna cewa kafin nunawa ga sakamako guda ɗaya na iya kara girman darajar wani fansa mai kayarwa, kamar yadda za'a sa ran idan akwai tushen kwayoyin da aka raba (misali, ΔFosB) na farfadowa na sakamako. Misali da wannan binciken, mata masu naman alade a baya an nuna su game da halayen jima'i suna nuna ingantattun hankulan su ga halin halayen cocaine (Bradley da Meisel, 2001). Wadannan binciken suna tallafawa ra'ayi na filastik a cikin ƙwararrayar sakamakon layin kwakwalwa, a cikin cewa an kiyasta farashin sakamako na yanzu a kan tallan da suka gabata.
A taƙaice, aikin da aka gabatar a nan ya ba da shaida cewa, baya ga magunguna na cin zarafi, sakamakon lada na haifar da matakin ΔFosB a cikin NAc. Hakazalika, cin zarafi na ΔFosB a cikin wannan kwakwalwar kwakwalwa yana tsara tsarin halayen dabba a sakamakon ladabi kamar yadda aka lura a baya don sakamako na miyagun ƙwayoyi. Wadannan binciken sun nuna cewa ΔFosB yana taka muhimmiyar rawa wajen tsara tsarin kayan aikin, kuma zai iya taimakawa wajen daidaita mahimmanci da aka gano a duk nau'o'in miyagun ƙwayoyi da kuma sakamakon ladabi. Har ila yau, sakamakonmu ya haifar da yiwuwar cewa ΔFosB shigarwa a cikin NAc na iya magance ba kawai bangarorin ɓangaren maganin miyagun ƙwayoyi ba, har ma da wasu abubuwan da ake kira fasikanci na halitta wanda ya shafi amfani da kyauta na dabi'a.
Godiya
Wannan aikin ya goyan bayan taimakon daga Cibiyar Nazarin Harkokin Lafiya ta Duniya da Ƙungiyar Ƙasa ta Kasa akan Drug Abuse da kuma Ƙungiyar Ƙasa ta Duniya don Bincike a Schizophrenia da Dama.
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