Ho khaotsa ho etsa hore ho be le mekhoa e fapaneng ea polelo ea FosB / ΔFosB ho tse ling tse tloaelehileng tsa Switzerland tse tsejoang e le tse ka hlahelang le tse hanyetsanang le tlhahiso ea motlakase e entsoeng ka ethanol (2014)

Keywords

• FosB;
• DeltaFosB;
• Senomotor sensitization;
• Ho khaotsa;
• Ho fapana ha boitšoaro;
• Litoeba

1. Selelekela

Phephetso ea lipatlisiso tsa morao-rao ea phekolo ea lithethefatsi ka ho lemalla lithethefatsi ke ho utloisisa mekhoa ea lipulasetiki ea neuronal e fetolang phetoho ea ho ithabisa ho fihlela ho lahleheloa ke boits'oaro ba boitšoaro mabapi le ho batla lithethefatsi le ho nka lithethefatsi. E 'ngoe ea likhopolo tsa bohlokoa ka ho fetisisa tsa ho lemalla lithethefatsi, tse bitsoang "lehlakoreng le letšo la tahi", e fana ka maikutlo a hore ho na le tsoelo-pele e tsoang ho ho se ts'oanehe (ho amana le ho matlafatsoa hantle) ho qobelloa ho tsitsisa (ho amana le ho matlafatsoa hampe). Ts'ebetso ena, ka potoloho e oeleng, e na le lintlha tse latelang: ho ameha / ho lebella, ho noa joala, le ho tlohela / ho senya (Koob le Le Moal, 2005, Koob le Le Moal, 2008 'me Koob le Volkow, 2010). Ho latela boemo bona, lithuto tsa lithethefatsi tsa lithethefatsi li 'nile tsa lebisa tlhokomelo mekhoeng ea methapo ea pelo e amanang le maikutlo a nyahamisang maikutlong a tsoang boemong bo boima le bo tsoelang pele. Ho ea ka khopolo ea "lehlakore le lefifi la tahi", ho bonahala eka ho etsahala liphetoho tsa nakoana ka nako e telele le tse sa tsitsang tsa polasetiki ka lipotoloho tsa neural tse batlang ho fokotsa moputso. Leha ho le joalo, liphetoho tsena tsa polasetiki li lebisa boemong bo nyahamisang ba maikutlo bo hlahang ha monyetla oa ho fumana lithethefatsi o thibeloa. Mokhoa ona o fane ka motlakase o matla oa ho tsuba, hammoho le, bakeng sa tlhokomelo ea oona (Koob le Le Moal, 2005 'me Koob le Le Moal, 2008).

Ho utloahala hohle hohle ke phoofolo ea bohlokoa ea liphoofolo e itšetlehileng ka taba ea hore ho eketsa liphello tse ikhethang tsa lithethefatsi nakong ea ho pepeseha ha tsona hangata ho tšoana le ho eketseha ha liphello tse bakoang ke lithethefatsi tse susumetsang batho ba nang le lithethefatsi (Vanderschuren le Kalivas, 2000 'me Vanderschuren le Pierce, 2010). Le hoja ho hlohlelletsoa ha mohaho ha ho etsise boitšoaro bo 'maloa bo amanang le ho lemalla lithethefatsi, likarolo tsa eona tsa nakoana tsa morphological le tsa methapo ea matšoao li tšoana le tse lebisang phetoho ea ho ithabisa ho ea lithethefatsi ka boeona (Robinson le Kolb, 1999, Vanderschuren le Kalivas, 2000 'me Vanderschuren le Pierce, 2010). Ka tloaelo, mokhoa oa ho hlohlelletsa batho ba nang le lisebelisuoa o na le mekhahlelo e meraro: ho fumana (ho pheta-pheta lithethefatsi), nako ea ho tlohela le phephetso (ho kopana le sethethefatsi ka mor'a nako ea ho tlohela). Ka bomalimabe, boholo ba liphuputso tse sebelisoang ke ho hlohlelletsoa hohle ho tsepamisitse mohopolo li lebisitse feela ho fumana le ho phephetsa mohato, ho kopanya nako ea ho tlohela mosebetsi.

Ho totobetse hore ho pepesehela lithethefatsi tsa tlhekefetso (Perrotti et al., 2008) le khatello ea kelello e sa foleng (Perrotti et al., 2004) ho eketsa polelo ea ntho e ngotsoeng fosB / deltafosB tsamaisong ea lik'hemik'hale. FosB / DeltaFosB ho bokella libakeng tsena e fetiselitsoe hore e phethe karolo ea bohlokoa ho tiisetsang khatello ea kelello (Berton et al., 2007 'me Vialou et al., 2010) le liphello tse putsang tsa cocaine (Harris et al., 2007 'me Muschamp et al., 2012), ethanol (Kaste le al., 2009 'me Li et al., 2010), le li-opioids (Zachariou et al., 2006 'me Solecki et al., 2008). Ka lebaka leo, ho ka khoneha hore FosB / DeltaFosB e hlophise liketsahalo tse ling tsa polasetiki tsa neuronal tse amanang le ho hlohlelletsoa ha motlakase oa ethanol, hammoho le ho tlosoa ha nako e ntseng e tsoela pele ho fumana mohato oa ho fumana tlhokomelo ea thekiso.

Hoa hlokomeleha hore ho na le liphapang tse fapaneng nakong ea phetoho ho tloha ho ts'ebeliso ea boithabiso le ho lemalla lithethefatsi (Flagel et al., 2009, George le Koob, 2010 'me Swendsen le Le Moal, 2011). Mohlala, litoeba tsa DBA / 2 J li sekametse ho arabeng ho feta C57BL / 6 J ho hlohlelletsoang ke locomotor sensitization (Phillips le al., 1997 'me Melón le Boehm, 2011a). Lintlheng tse ling tsa tlhaho tsa Switzerland, tlhahiso ea boitšoaro mabapi le ho hlohlelletsoa ha batho ba nang le ethanol e ile ea hlalosoa ka lekhetlo la pele ka Masur le dos Santos (1988). Ho tloha ka nako eo ho ea pele, lipatlisiso tse ling li bontšitse likarolo tsa bohlokoa tsa methapo ea methapo e amanang le ho fetoha ha boitšoaro ho fumanoeng ho hlohlelletsoa ha motlakase oa ethanol (Souza-Formigoni et al., 1999, Abrahão et al., 2011, Abrahão et al., 2012, Quadros et al., 2002a 'me Quadros et al., 2002b). Leha ho le joalo, lipatlisiso tsena ha lia ka tsa sebetsana le liphello tsa ho fetoha ha boitšoaro nakong ea nako ea ho tlohela nako ka mor'a hore ho fumanoe mohato oa ho fumana tšebetso ea mohahlauli. Phuputsong ea morao tjena, laboratori ea rona e hlalositse phapang e kholo pakeng tsa litoeba tsa Switzerland tse hlokomelisitsoeng le tse sa utloisiseng mabapi le polelo ea mofuta oa cannabinoid receptor mofuta oa 1 (CB1R) nakong eohle ea ho tlosoa. Phuputsong eo, litoeba tse hlokomelisitsoeng (empa e se tse sa amohelehang) li ne li eketsehile polelo ea CB1R sebakeng sa prefrontal cortex, sebaka sa ventral tegmental, amygdala, striatum le hippocampus (Coelhoso et al., 2013).

Ha ho fanoa ka phapano e sa fetoheng ea boits'oaro ho litoeba tsa Switzerland tse fetelletseng mabapi le ts'ehetso ea ethomol e hlohlelletsoang ke ethanol, le hore phapang ena e tsamaea le likarolo tse ikhethileng tsa methapo ea kutlo nakong ea ho tlohela, thuto ea hajoale e batlisitse polelo ea FosB / DeltaFosB litoeba tse khothatsang le tse sa khothatsang qalong (18 h) le kamora matsatsi a 5 a ho tlohela.

2. Boitsebiso le mekhoa

2.1. Lihlooho

Ho ile ha sebelisoa litoeba tsa banna tse tsoang Switzerland tsa Switzerland (EPM-1 Colony, São Paulo, SP, Brazil), eo qalong e neng e tsoa moleng oa Albino Swiss Webster ho tsoa Setsing sa Ntlafatso ea Mefuta ea Liphoofolo ho Biology le Bongaka ho la Universidade Federal de São Paulo. . Litoeba li ne li le libeke tse 12 (30-40 g) ha li qala. Lihlopha tsa litoeba tse 10 li ne li lula ka masakeng (40 × 34 × 17 cm) ka libethe tsa woodchip. Mocheso (20-22 ° C) le mongobo (50%) kolone ea liphoofolo e laoloang e ile ea bolokoa ka potoloho e bobebe / e lefifi (12/12 h), mabone a bonesitsoe ka 07:00 h, a e-na le likhokoane tsa toeba le lipapatso tsa metsi libitum, ntle le nakong ea liteko. Litoeba li ile tsa bolokoa maemong ana a bolulo bonyane matsatsi a 7 pele ho kalafo ea lithethefatsi le liteko tsa boits'oaro. Tlhokomelo ea liphoofolo le lits'ebetso tsa liteko li ile tsa etsoa tlasa melaoana e amohetsoeng ke Komiti ea Boitšoaro ba Liphoofolo le Ts'ebeliso ea Yunivesithi (nomoro ea protocol: 2043/09), ho latela EU Directive 2010/63 / EU bakeng sa liteko tsa liphoofolo (http://ec.europa.eu/environmental/chemicals/lab_animals/legislation_en.htm).

2.2. Senomotor sensitization

Tsamaiso ea ts'ebetso ea ho holisa e ne e itšetlehile ka thuto e fetileng ho laboratori ea rona (Coelhoso et al., 2013). Qalong ea protocol, liphoofolo tsohle li ile tsa entoa ka letsoai (ip) ka letsoai 'me hang-hang tsa lekoa ka lebokoseng la ts'ebetso (Insight, Brazil) bakeng sa 15 min ho theha basal locomotion. Matsatsi a mabeli hamorao, liphoofolo li ne li kenoa letsatsi le letsatsi ka ethanol (2 g / kg, 15% w / v ho 0.9% NaCl, ip - EtOH sehlopha, N = 40) kapa letsoai (molumo o tšoanang, ip, - Sehlopha sa taolo, N = 12), nakong ea matsatsi a 21. Hang feela kamora liente tsa 1, 7, 14, le 21st, liphoofolo li ile tsa beoa ka lebokoseng la ts'ebetso bakeng sa 15 min. Boemo bo otlolohileng boemong bo bong le bo bong bo lekantsoe ke sistimi ea tlhahlobo ea boits'oaro (Pan Lab, Spain). Joalo ka ha ho lebelletsoe ( Masur le dos Santos, 1988 'me Coelhoso et al., 2013), mekhoa e fapaneng ea boitšoaro mosebetsing oa letsatsi le leng le le leng la 21 e re lumella ho abela liphoofolo tsa EtOH likarolong tse ling tsa 2: EtOH_High (e nkiloeng ho tsoa 30% ea ho tsamaisa) le EtOH_Low (e nkiloeng ho 30% ea tlaase ea ho aba). Ka hona, ke feela liphoofolo tsa 60% tse kenyelletsoeng tlhahlobo. Mokhoa ona o ts'oana le o sebelisitsoeng lipatlisisong tsa ho hlahloba phapang ea motho ka har'a paradigm e matlafatsang ethanol ( Masur le dos Santos, 1988, Souza-Formigoni et al., 1999, Quadros et al., 2002a, Quadros et al., 2002b, Abrahão et al., 2011, Abrahão et al., 2012 'me Coelhoso et al., 2013).

Kamora tlhophiso e hlalosang lihlopha tsa liteko, re ile ra etsa liteko tse 2 tse ikemetseng ho latela maemo a nakoana a nako ea ho hula: (i) liphoofolo tse tlisitsoeng mokhatlong oa phumano 'me tsa etsoa sehlabelo kamora h 18 ea ho hula le (ii) liphoofolo tse tlisitsoeng molemong oa phumano le ho etsa sehlabelo kamora matsatsi a 5 a ho tlohela. Kahoo, phuputso ena e ne e na le lihlopha tsa liteko tsa 3 (Control, EtOH_High, le EtOH_Low) tse neng li arotsoe ka lihlopha tse 2 (18 h le matsatsi a 5 a ho tlohela) (N = 6 sehlopheng ka seng). Khetho ea matšoao ana a mabeli a nako nakong ea ho tlohela e ne e le ka lebaka la likarolo tsa kinetic tsa polelo ea FosB le DeltaFosB kamora 18 h ea ho tlohela (joalo ka ha ho hlalositsoe karolong ea lipuisano), le kamora matsatsi a 5 a ho tlohela, ho ipapisitse le lithuto tse fetileng tsa Lab ea rona e batlileng likarolo tse ling tsa methapo ea kutlo mabapi le nako ea ho hula kahare ho paradigm ea sensomotor sensitization ( Fallopa le al., 2012 'me Escosteguy-Neto le al., 2012). Kamora nako, ho etsa likamano lipakeng tsa sensitization ea locomotor le polelo ea FosB / DeltaFosB, re balile lintlha tsa sensitization ea locomotor bakeng sa phoofolo ka 'ngoe, ka foromo: score = (Locomotion ka letsatsi la 21 - Locomotion ka letsatsi la 1st) * 100 / Locomotion in the Letsatsi la 1.

2.3. Immunohistochemistry

Kamora nako e ikhethileng ea ho hula, liphoofolo li ile tsa thethesoa ka ho teba ka jarekete e nang le ketamine (75 mg / kg, ip) le xylazine (25 mg / kg, ip). Kamora ho lahleheloa ke corneal reflex, ba ile ba tlotsoa ka monko o monate ka 100 ml ea phosphate buffer solution 0.1 M [phosphate buffered saline (PBS)], e lateloa ke 100 ml ea 4% paraformaldehyde (PFA). Boko bo ile ba tlosoa hang kamora ho tšeloa metsi, ho bolokoa ho PFA bakeng sa 24 h ebe ho bolokoa tharollo ea 30% ea sucrose / PBS bakeng sa 48 h. Likarolo tsa serial coronal (30 μm) li ile tsa khaoloa ho sebelisoa microtome e hoammeng 'me tsa bolokoa kahare ho tharollo e thibelang leqhoa hore e sebelisoe lits'ebetsong tsa immunohistochemistry ka ho silafatsa mahala.

Bakeng sa immunohistochemistry, mokhoa o tloaelehileng oa avidin – biotin – immunoperoxidase o ile oa etsoa. Likarolo tsa boko ba lihlopha tsohle tsa liteko li kenyelelitsoe ts'ebetsong e le 'ngoe, li entsoe pele ka hydrogen peroxidase (3%) bakeng sa 15 min ebe li hlatsuoa ka PBS bakeng sa 30 min. Ebe likarolo tsohle li pepesitsoe nakong ea metsotso e 30 ho PBS-BSA .5% ho qoba ho arabela ka tsela e sa tobang. Kamora moo, likarolo li ile tsa koaheloa ka bosiu bo le bong le anti-FosB / DeltaFosB ea mantlha ea anti-antibody (1: 3,000; Sigma Aldrich, St Louis, MO, USA no.cat. AV32519) ka tharollo ea PBS-T (30 ml PBS, 300 μl Triton X-100). Kamora moo, likarolo li ile tsa kenyelletsoa 2 h ka lesole la mmele la bobeli la anti-mmutla IgG (1: 600; Vector, Burlingame, CA, USA) mocheso oa kamore. Likarolo tseo li ile tsa alafshoa ka avidin-biotin complex (Vectastain ABC Standard kit; Vector, Burlingame, CA, USA) bakeng sa 90 min mme ea romelloa karabong e matlafalitsoeng ea nickel ea diaminobenzidine. Pakeng tsa methati, likarolo li ile tsa hlatsuoa PBS mme tsa tsukutleha ho rotator. Likarolo li ne li behiloe holim'a li-slide tse tlotsitsoeng ka gelatin, li omisitsoe, li felloa ke metsi 'me li koahetsoe.

Libaka tse latelang tse entsoeng ka marang-rang li ile tsa hlahlojoa: prefrontal cortex [pele-pele e nang le cortex (Cg1), prelimbic cortex (PrL) le infralimbic cortex (IL)], motor cortex [sekhahla (M1) le sekete (M2)], dorsal striatum [dorsomedial striatum ( DmS) le dorsolateral striatum (DlS)], ventral striatum [nucleus accumbens core (Acbco) le shell (Acbsh), ventral pallidum (VP)], hippocampus [pyramidal layer ea Cornus Ammong 1 le 3 (CA1 le CA3, ka ho latellana), sekhahla sa granular sa dentate gyrus (DG)], amygdala [basolateral nucleus (BlA), le nucleus central (CeA)], mokokotlo oa lik'hemik'hale oa hypothalamus (VMH) le sebaka sa ventral tegmental [anterior (VTAA) le likarolo tsa posterior (VTAP) Bona Setšoantšo sa 1). Ho ile ha sebelisoa microscope ea Nikon Eclipse E200 e hokahantsoeng le komporo ho nka litšoantšo tse tsoang karolong ka 'ngoe ho holisa × 20. Litšoantšo li bolokiloe joalo ka li-archives tsa .tiff bakeng sa tlhahlobo ea morao-rao ea boits'ireletso ba mmele ba FosB / DeltaFosB. Lisele tse sa sebetseng li ne li baloa ho sebelisoa software ea ImageJ (NIH Image, Bethesda, MD, USA). Libaka tsa boko li ne li hlalositsoe setšoantšong ka seng ho latela Stereotaxic Mouse Brain Atlas (Franklin le Paxinos, 1997). Ho tloha ha li-photomicrographies tse nkuoeng ka microscope li emela 2.5 × 10³ μm² ka ho holisa 20 ×, palo ea lisele tse ngoliloeng ka FosB / DeltaFosB e hlahisoa e le karolelano ea lisele tse sireletsang mmele ka 2.5 × 10³ μm². Litekanyetso tse fumanoeng lihlopheng tsa EtOH li ile tsa hlophisoa ka boleng ba taolo, 'me tsa hlalosoa e le%. (Taolo = 100%).

2.4. Tlhahlobo ea statistical

Pele, Shapiro-Wilk e ne e sebelisetsoa ho netefatsa tloaelo ea kabo ea mefuta eohle. Liphetho tsa boits'oaro li ile tsa hlahlojoa ke ANOVA ea tsela e le 'ngoe bakeng sa litekanyo tse phetoang tse nkoang e le lisosa tsa linako tsa 5 tsa sensitization ea locomotor: basal, letsatsi 1, letsatsi 7, letsatsi 14 le letsatsi 21. Liphetho tsa histological li ile tsa hlahlojoa ke ANOVA ea litsela tse peli, ho nahanoa e le mabaka: nako ea ho hula (matsatsi a 18 le matsatsi a 5) le sehlopha sa liteko (Taolo, EtOH_High le EtOH_Low). Mefuta-futa ea li-nonparametric e ne e behiloe maemong a Z ho fokotsa ho hasana ha data, ebe e sebelisoa ka tsela ea ANOVA, joalo ka ha ho hlalositsoe pejana. Newman Keuls post-hoc e ne e sebelisoa ha ho hlokahala. Kamora nako, re ile ra batlisisa likamano tse ka bang teng lipakeng tsa lisele tse ntle tsa FosB / DeltaFosB le bohloeki ba locomotor. Likamano tsena li ne li baloa feela bakeng sa li-nuclei moo liphapang tsa lipalo lipakeng tsa lihlopha tsa liteko li fumanoeng. Hobane liphapang tsena li ne li lekanyelitsoe matsatsing a 5 a ho khaotsa (Bona karolo ea liphetho), litekanyetso tsa FosB / DeltaFosB tse nkoang likopanong tsena li bua ka nako ena e ikhethang ea ho khaotsa. Hobane liphapang tsena li ne li lekanyelitsoe matsatsing a 5 a ho khaotsa (Bona karolo ea sephetho), litekanyetso tsa FosB / DeltaFosB tse nkoang likopanong tsena li bua ka nako ena ea ho tlohela. Boemo ba bohlokoa bo behiloe ho 5% (p <0.05).

3. Liphetho

3.1. Senomotor sensitization

HO ETSA bakeng sa mehato e phetoang e fumaneha phapang e khōlō sehlopheng sa sehlopha [F_(2,32) = 68.33, p <0.001], nakong ea protocol [F_(4,128) = 9.13, p <0.001], le tšebelisano lipakeng tsa bona [F_(8,128) = 13.34, p <0.001]. Ho ne ho se na liphapang khoebong ea basal, 'me lihlopha ka bobeli tsa EtOH li bile le keketseho e ts'oanang ea locomotion ka letsatsi la pele la theko, ha li bapisoa le sehlopha sa Control (p <0.01). Leha ho le joalo, EtOH_High (empa eseng EtOH_Low) e hlahisitse keketseho e tsoelang pele ea tšebetso ea locomotor ho pholletsa le mohato oa ho fumana (p <0.01, mabapi le lihlopha tsa Control le EtOH_Low, letsatsing la ho qetela la theko; p <0.01 mabapi le ts'ebetso ea eona ea locomotor ka letsatsi la pele la phumano) ( Setšoantšo sa 2). Lintlha tsena li tšehetse liphello ho tsoa thutong ea pele ( Masur le dos Santos, 1988) le ho tsoa tlalehong ea rona e fetileng ( Coelhoso et al., 2013) mabapi le mekhoa e fapaneng ea boits'oaro bo hlahang litlhapi tsa Switzerland tse tsamaisitsoeng ho matlafatsoa ha lits'enyehelo tsa ethanol.

3.2. Puo ea FosB / DeltaFosB

Photomicrographics ea papiso ea FosB / DeltaFosB e se nang boits'oaro e hlalositsoe Setšoantšo sa 3 'me litekanyetso tse tloaelehileng li bonts'itsoe Setšoantšo sa 4, Setšoantšo sa 5, Setšoantšo sa 6 'me Setšoantšo sa 7. Tsela e 'meli ANOVA e hlokometse phapang e khōlō M1, M2, DmS, DlS, Acbco, Acbsh, VP le VTA (bakeng sa litekanyetso tse sa tloaelehang tsa FosB / DeltaFosB ho se sebetse hantle le ho hlahloba lintlha tsa mekhoa eohle, bona Lethathamo la Tablex1 'me Tafole 1, ka ho latellana). Ka likarolo tseo liphapano tsa lipalo li ka bonoang ho tsona, ho ne ho na le mekhoa e mene e fapaneng ea polelo ea FosB / DeltaFosB. Ho ea pele, e hlokometsoeng ho M1 le M2, ho bile le keketseho ea polelo ea FosB / DeltaFosB ka letsatsi la bohlano la ho tlosoa ha ethanol feela sehlopheng sa EtOH_High (ha ho bapisoa le litekanyetso tsa EtOH_High ho 18 h ea ho khaotsa, hape le ho Taolo le lihlopha tsa EtOH_Low matsatsing a 5 a ho tlohela mosebetsi (bona Setšoantšo sa 4). Mofuteng oa bobeli, o hlokometsoeng ho VTAA, polelo ea FosB / DeltaFosB e eketsehile matsatsing a 5 a ho tlosoa ha ethanol sehlopheng sa EtOH_Low (ha ho bapisoa le litekanyetso tsa EtOH_Low ho 18 h ea ho khaotsa, hammoho le ho sehlopha sa Taolo matsatsing a 5 a ho tlohela ) (bona Setšoantšo sa 5). Mofuteng oa boraro, o hlokometsoeng ho polelo ea DmS, Acbco, le Acbsh, FosB / DeltaFosB e eketsehile matsatsing a 5 a ho tlosoa ha ethanol lihlopheng ka bobeli tsa EtOH_High le EtOH_Low (ha li bapisoa le litekanyetso tsa tsona ka 18 h ea ho tlohela), leha ho le joalo, ke sehlopha sa EtOH_Low feela e fapane le sehlopha sa Taolo (bona Setšoantšo sa 6). Kamora nako, ka mokhoa oa bone, o hlokometsoeng ho DlS le VP, polelo ea FosB / DeltaFosB e eketsehile matsatsing a 5 a ho tlosoa ha ethanol lihlopheng ka bobeli tsa EtOH_High le EtOH_Low (ha ho bapisoa le litekanyetso tsa tsona ka 18 h ea ho tlohela), leha keketseho ena e ne e hlakisa haholoanyane ho EtOH_Low ho feta sehlopha sa EtOH_High, mme ke sehlopha sa EtOH_Low feela se fapaneng le sehlopha sa Control (bona Setšoantšo sa 7).

Ho tiisa hore liphetoho FosB / DeltaFosB li ne li bakoa ke ho tlosoa, 'me ha li hlahisoe ke ethanol, re ile ra etsa likamano pakeng tsa lintlha tsa tlhahiso-kholiso ea lisebelisoa le lisele tsa FosB / DeltaFosB tsa immunolabelled ka letsatsi la 5th la ho tlosoa ka nuclei e boletsoeng ka holimo (M1, M2, Acbco, Acbsh, DmS, DlS, VP, VTAA). Joalokaha ho lebeletsoe, ho ne ho se na likamano tse bohlokoa bakeng sa leha e le efe ea li-nuclei tsena (M1 - r² = 0.027862, p = 0.987156; M2 - r² = 0.048538, p = 0.196646; Acbco - r² = 0.001920, p = 0.799669; Acbsh - r² = 0.006743, p = 0.633991; DmS - r² = 0.015880, p = 0.463960; DlS - r² = 0.023991, p = 0.914182; VP - r² = 0.002210, p = 0.785443; VTAA - r² = 0.001482, p = 0.823630).

4. Puisano

Liphetho tse fumanoeng phuputsong ea hona joale li bontša hore polelo e ntseng e eketseha ea FosB / DeltaFosB e boletsoeng ka paradigm e hlohlelletsoang ke motlakase ea ethanol e ka 'na ea amahanngoa le ho tlohela ho e-na le hore e be e sa foleng lithethefatsi. Leha ho le joalo, ho fapana ha boitšoaro boemong ba nts'etsopele ea ho nts'etsopele ho ne ho tsamaisana le mekhoa e khethollang ea FosB / DeltaFosB polelo nakong ea ho tlohela. Karolo ea motlakase oa motlakase, sebaka sa ventral tegmental le striatum ha ho fumanoa le ho buuoa ha phallo ea ho matlafatsa mohaho o thehiloe hantle (Vanderschuren le Pierce, 2010). Ho feta moo, ho khetholloa ha litsela tsa maoto ke e 'ngoe ea lihlooho tsa methapo ea pelo ea ho tlohela nako, hammoho le ho hlaha ha amygdala (Koob le Le Moal, 2005 'me Koob le Le Moal, 2008). Leha ho le joalo, liphuputso tse fokolang feela li ile tsa hlahloba nako ea ho tlosoa ha paradigm ea ho hohela. Liphello tsa rona li ile tsa kopana le liphetoho tse thahasellisang FosB / DeltaFosB polelo ea motlakase, sebaka sa ventral tegmental le striatum nakong ena.

FosB cDNA e kenyelletsa polelo ea liprotheine tsa 33, 35 le 37 kDa. Ho pepeseha ha 'mele ka matla ho lebisa ho matla ho 33- le discrete 35- le 37- kDa Fos protein induction. Ka lebaka leo, tlasa ts'ebetso e matla, polelo e hlahelletseng ea FosB e amana le 33 kDa (McClung et al., 2004 'me Nestler, 2008). Ho na le phapang e ngoe e makatsang lipakeng tsa liprotheine tsena: ke liprotheine tse 35-37 kDa feela tse tsitsitseng li-isoforms. Ka lebaka la botsitso bona bo phahameng, mefuta ena ea FosB e khaotsoeng, eo hape e bitsoang DeltaFosB, e bokellana bokong mme e hlahisoa haholo ho arabela litšitiso tse sa foleng, joalo ka kalafo ea lithethefatsi tsa psychotropic, ho tšoaroa ke motlakase o sa foleng le khatello ea maikutlo (Kelz le Nestler, 2000, Nestler et al., 2001 'me McClung et al., 2004). Ka lebaka leo, DeltaFosB e 'nile ea nkoa e le mokhoa o tsitsitseng oa limolek'hule bakeng sa ho kopanya mefuta e mengata ea polasetiki ea neural le ea boitšoaro e tšoarellang nako e telele. Ho thahasellisang ke hore thuto e hlollang ka ho sebelisa melapo ea mela e bontšang ka tsela e fapaneng FosB le DeltaFosB li bontšitse hore FosB ke ea bohlokoa bakeng sa ho matlafatsa khatello ea kelello le ho senya kamano pakeng tsa ho khothaletsoa ha lisebelisoa tsa psychostimulant le ho bokella DeltaFosB ho striatum (Ohnishi et al., 2011). Ka hona, liprotheine ka bobeli li ka bapala karolo ea bohlokoa ho protocol ea liteko e sebelisitsoeng thutong ea hajoale. Hoa hlokomeleha hore lesole la 'mele la FosB le sebelisitsoeng le amohela FosB le DeltaFosB ka bobeli. Ho tloha ha FosB e theohela maemong a mantlha kahare ho 6 h kamora ho hlasimoloha ho matla (Nestler et al., 2001) mme DeltaFosB e bokellana kamora ho pepesetsoa makhetlo a mangata, re nkile qeto ea ho nyehela liphoofolo 18 h kamora mohato oa ho fumana, ho qoba khethollo ea kalafo ea ethanol ka lebaka la polelo ea FosB. Leha ho le joalo, ho nepahala ka setegeniki, re tla bua thutong ea hajoale e le polelo ea FosB / DeltaFosB. Ho bohlokoa ho hlokomela hore leano lena le sebelisitsoe lipatlisisong tse ling, ho kenyeletsoa le tse sebelisitseng antibody e le 'ngoe ea mantlha e hlalositsoeng mona (Fetola le al., 2008, Li et al., 2010, Flak et al., 2012 'me García-Perez et al., 2012). Ka lebaka leo, ntle le mefokolo ena ea liteko, re tla tšohla liphello tsa rona ho nahana ka karolo ea DeltaFosB ka lipulasetiki tsa neuronal.

Ho totobetse hore ho itšireletsa ha lithethefatsi tse sa foleng ho eketsa polelo ea FosB / DeltaFosB libakeng tse 'maloa tsa boko (Nestler et al., 2001 'me Perrotti et al., 2008). Ho makatsang ke hore phuputsong ea hajoale, litoeba tsa ethanol tse sa matlafatseng kapa tsa litoeba li sa tšoane le litoeba tse sa foleng tse nang le letsoai mabapi le polelo ea FosB / DeltaFosB 18 h kamora mohato oa ho fumana. Ntle le moo, ho ne ho se na likamano tse bohlokoa lipakeng tsa polelo ea FosB / DeltaFosB le bohloeki ba locomotor. Phapang ena e ka hlalosoa, bonyane hanyane, ke liphapang tse fumanoang ho protocol ea liteko. Mohlala, ha ho nahanoa ka ponahalo ea ethanol, lithutong tse peli paradigm e 'meli ea khetho ea mahala e sebelisitsoe linakong tse 15 tsa ho noa nako le nako (Li et al., 2010) kapa phepo e felletseng ea phepelo ea mokelikeli e laoloang ka boiketsetso nakong ea matsatsi a 17 (moo liphoofolo li jang ethanol ka tekanyetso ho tloha ho 8 ho isa ho 12 g / kg / ka letsatsi) (Perrotti et al., 2008). Phuputsong e 'ngoe, le hoja bangoli ba bua ka phekolo e sa foleng, protocol e ne e e-na le likhetho tsa 4 ethanol feela (Ryabinin le Wang, 1998). Kahoo, melaoana e sebelisoang libakeng tse ling e fapane ka ho felletseng le e sebelisitsoeng mona, e neng e na le matsatsi a 21 a kalafo moo liente tsa letsatsi le letsatsi tsa ethanol li neng li tsamaisoa ke liteko. Leha ho na le liphapang tsena, ho na le liphuputso tse 'maloa tse kenyelletsang liente tsa intraperitoneal tse tlalehang keketseho ea polelo ea FosB / DeltaFosB kamora melaoana ea ts'usumetso ea locomotor e hlohlellelitsoeng ke li-psychostimulants (Brenhouse le Stellar, 2006, Fetola le al., 2008 'me Vialou et al., 2012) le li-opioids (Kaplan et al., 2011). Leha ho le joalo, mekhoa ea ho khothaletsoa ha lits'ebetso tse joalo li kenyeletsa ho fokotsa lithethefatsi tsa 21, 'me ho tse ling tsa tsona, lithethefatsi li ne li tsamaisoa ka tsela e ka hare. Ka lehlakoreng le leng, protocol ea rona e sebelisitse phekolo e tšoanang e hlalositsoeng liphuputsong tse fetileng tse amanang le 21 letsatsi le leng le le leng liente tsa ethanol (Masur le dos Santos, 1988, Souza-Formigoni et al., 1999, Quadros et al., 2002a, Quadros et al., 2002b, Abrahão et al., 2011 'me Abrahão et al., 2012). Ho na le bopaki ba hore le hoja tsamaiso e sa tloaelehang ea cocaine e khothalletsa ho bokellana ha DeltaFosB polelo e nucleus accumbens, e boetse e khothalletsa ho mamella DeltaFosB mRNA ho kenya letsoho ka bobeli ventral le dorsal striatum (Larson et al., 2010). Ka lebaka leo, re ne re nahana hore ho se lumellane ha lihlopha tsa rona tsa liteko ka karolo ea ho reka ho ka 'na ha e-ba ka lebaka la ho mamelloa mabapi le ho fokolloa ha FosB / DeltaFosB, kaha tsamaisong ea hona joale e ne e le nako e kholo ea ho fumana phaello ho bapisoa le linako tse sebelisetsoang psychostimulant le opioids lithuto tse ling.

Liphuputso tse sebelisang litoeba tsa ho kokota le tse ling tsa tlhaho li bontšitse hore litoeba tsa FosB tse tsitsitseng li ntlafalitse boitšoaro ba lik'hok'heine, tse kang liphello tse tsosang takatso le sebaka se khethiloeng sebakeng seo. Ho feta moo, polelo ea DeltaFosB ea basal le ea cocaine-inducible ha e eo ho eona litoeba tse feto-fetohang (Hiroi et al., 1997). Ka lehlakoreng le leng, litoeba tsa maiketsetso tse nang le ts'oaetso e feteletseng ea DeltaFosB pontšo e ile ea eketsa kutloisiso ea liphello tse khotsofatsang tsa cocaine le morphine (Muschamp et al., 2012). Liphetho tsena li fana ka bopaki bo tobileng ba ho lumellana ho haufi pakeng tsa DeltaFosB le mokhoa o khotsofatsang. Ntle le ho pepeseha ha lithethefatsi khafetsa, khatello ea maikutlo e sa foleng e boetse e eketsa polelo ea DeltaFosB ka lipotoloho tse sebetsang hantle (Perrotti et al., 2004). Ho thahasellisang ke hore litlhapi tse ngata tse hlaselang DeltaFosB ha li fokotsehe haholo ka liphello tse sithabetsang tsa kappa-opioid agonist, tse tsejoang ho hlahisa dysphoria le likhatello tse kang khatello ea litoeba (Muschamp et al., 2012). Kahoo, ntle le ts'ebetso ea moputso, DeltaFosB le eona e bapala karolo ea bohlokoa maemong a maikutlo a liketsahalo. Boemong bona, ho ikhula ho ka baka polelo ea FosB / DeltaFosB, hobane khatello ea maikutlo ke karolo ea bohlokoa ea ho tlohela lithethefatsi. Pono ena e latela liphetho tsa rona, hobane ho ne ho se na likamano lipakeng tsa polelo ea FosB / DeltaFosB le bohlohlelletsi bo bongata, mme keketseho ea polelo ea FosB / DeltaFosB e bonoe feela ka letsatsi la bohlano la ho tlohela.

Ho thahasellisang ke hore mekhatlong e meng, FosB / DeltaFosB e eketsehile e ile ea bonoa ho sehlopha sa EtOH_High le EtOH_Low, le hoja ho hlalositsoe ho feta sehlopha sa pele, ho fana ka maikutlo a hore keketseho ena e ka ba le liphello tse fapaneng tse sebetsang, ho latela matla a bona. Tlhahiso ena e ka hlalosoa ke mesebetsi e fapaneng e fapaneng e sebetsang ea FosB / DeltaFosB. Ka mohlala, likhofu tse neng li tšoaelitsoe ka cocaine li ekelitse polelo ea DeltaFosB nucleus accumbens nakong ea ho tlohela nako, phello e lumellana hantle le khetho ea li-cocaine, empa e fapane le khetho ea lichaba. Ho feta moo, ho imeloa kelellong nakong ea ho ikhula ho eketsa boitšoaro ba boitšoaro ho li-psychostimulants ka ho eketsa polelo ea DeltaFosB ka li-neurons tse fokolang maikutlo (Nikulina et al., 2012). Kahoo, DeltaFosB e ne e ka bolela esale pele ho fokotsa ho sebelisoa ha hedonic e hlahang nakong ea ho tlohela nako e telele (Marttila et al., 2007). Ka lehlakoreng le leng, bobeli ba ho imeloa kelellong le likarabo tse loantšang maikutlo li amana le tlhaloso e phahameng ea DeltaFosB ka striatum (Vialou et al., 2010). Ka hona, re nahana hore ho eketseha ha FosB / DeltaFosB ho statum e EtOH_Ho ho ka be ho ntlafalitse liphello tse khotsofatsang tsa ethanol, ho fana ka ts'oaetso e phahameng ho latela lithethefatsi. Ka lehlakoreng le leng, ho eketseha ho matla ho FosB / DeltaFosB ho sehlopha sa EtOH_Low ho ka be ho fokolitse kutloisiso ho bobeli ba dysphoria le khatello ea kelello, ho fokotsa liphello tse mpe tsa ts'ebeliso ea lithethefatsi tse latelang, ka lebaka leo, ho hlalosa khanyetso e phahameng ho sena sehlopha. Ho thahasellisang ke hore ho tsieleha hona ho ne ho e-na le methapo ea maikutlo. Ka mohlala, FosB e tloaelehileng ea litoeba tse sa tloaelehang tse nang le methapo ea mokokotlo ea GABAergic neurons ea nucleus accumbens e ne e eketsehile maemong a mabeli le a kappao- opioid (Sim-Selley et al., 2011), 'me li-receptor tseo li phahamisa le ho thibela molumo oa mesolimbic (Manzanares et al., 1991 'me Devine et al., 1993). Ho feta moo, polelo ea mofuta oa sele e ka boela ea fetola liphello tse sebetsang tsa ho eketsa FosB / DeltaFosB. Thupong e tsotehang ka ho sebelisa litoeba tse hlaselang DeltaFosB ho D1- kapa D2- li-neurons tse hlalosang nucleus accumbens li senoletse hore DeltaFosB ho D1- (empa e seng ka D2-) neurons e eketsa likarabo tsa boitšoaro ho cocaine (Grueter et al., 2013).

Ho makatsang ke hore mabapi le motor cortex, ho bile le keketseho ea polelo ea FosB / DeltaFosB feela sehlopheng sa EtOH_High, mme e ne e thibetsoe ho letsatsi la 5th la ho tlohela. Ho haella ha keketseho ho 18 h ea ho tlohela ho ka hlalosoa ke mokhoa o ka bang teng oa mamello ho polelo ea FosB / DeltaFosB sebakeng sena kamora ho pepeseha ha ethanol e sa foleng. Ntle le moo, liphetho tsa rona li fana ka maikutlo a hore ho na le liphetoho tse sebetsang tsa methapo ea kutlo ho motor cortex nakong ea ho tlohela, leha liphoofolo li sa ka tsa sebelisoa nakong ena. Sena sea khahlisa, hobane polasetiki ena e ka nka karolo, bonyane ka mokhoa o itseng, ho boloka ts'ehetso ea locomotor. Le ha hyperlocomotion e matlafalitsoeng kamora matsatsi a 'maloa a ho tlohela e sa ka ea ithutoa mona, ho na le lithuto tse' maloa, ho kenyeletsoa le tse fetileng tsa Lab ea rona, tse bonts'ang litoeba tse matlafalitsoeng (empa eseng tse sa matlafatsoang) li ntlafalitse locomotion ha li phephetsoa ka ethanol kamora nako ea ho tlohela (Masur le dos Santos, 1988, Souza-Formigoni et al., 1999, Quadros et al., 2002a, Quadros et al., 2002b, Abrahão et al., 2011, Abrahão et al., 2012, Fallopa le al., 2012 'me Coelhoso et al., 2013).

Qetellong, hoa hlokomeleha hore sehlopha sa EtOH_Low feela se bonts'itse polelo ea FosB / DeltaFosB e ntseng e eketseha ka karolo ea pele (empa e se posterior) ea sebaka sa ventral tegmental. Likarolo tsena li na le litekanyetso tse fapaneng le litlaleho tsa methapo ea kutlo, 'me ho kopanela ha bona molemong oa moputso ho itšetlehile ka lintlha tse' maloa (Kemoto, 2007). Mohlala, boitaolo ba likhoto ba ethanol bo amana le bokamorao, empa eseng le karolo e ka hare ea sebaka sa ventral tegmental (Rodd-Henricks le al., 2000 'me Rodd et al., 2004). Ho feta moo, tsamaiso ea endocannabinoid, hammoho le GABA-A, D1-D3, le serotoninergic 5HT3 receptors, e phetha karolo ea bohlokoa moetleng oa ho batla ethanol (Linsenbardt le Boehm, 2009, Rodd et al., 2010, Melón le Boehm, 2011b 'me Hauser et al., 2011). Leha ho le joalo, GABA-B e karolong e ka hare ea sebaka sa ts'ebetso ea morero e bohlokoa ho ea ka moputso (Moore le Boehm, 2009) le liphello tse tsosang takatso (Boehm et al., 2002) ea ethanol. Ho feta moo, li-receptor tse nang le li-nicotinic tse karolong e ka hare ea naha li kenyelelitsoe ho eketseha ha litekanyetso tsa dopamine tse bakoang ke ethanol (Ericson et al., 2008). Ka hona, ho sa tsotellehe bopaki bo hlakileng ba likarolo tsena, ho ka etsahala hore liphetoho tse bonoang sehlopheng sa EtOH_Low likarolong tse ling tsa pele li ka amana le mokhoa o khotsofatsang. Cocaine e sa foleng empa e se lefu le sa foleng kapa e sa foleng ea ho imeloa kelellong e eketsa DeltaFosB sebakeng sa ventral tegmental, haholo-holo sepaleng sa gamma-aminobutyric acid (GABA) (Perrotti et al., 2005). Taba ena e ka hlalosa maemo a tloaelehileng a FosB / DeltaFosB nakong eohle ea ho tlohela mekhoa ea ventral tegmental sebakeng sa EtOH_Hong litoeba, ho sa tsotellehe boiphihlelo bo matla ba khatello ea maikutlo nakong ena. Ho feta moo, boitsebiso bona bo lumellana, bonyane ka mokhoa o sa fellang, khopolo-taba ea hore ho eketseha ha FosB / DeltaFosB hohle ha ho tlosoa EtOH_Low ho ka khetholloa e le ho arabela habonolo.

Ho se tšoane ha batho ka bomong ho bonngoe nakong ea phetoho ea tšebeliso ea boithabiso ho tsuba lithethefatsi ho tsoteha (Flagel et al., 2009, George le Koob, 2010 'me Swendsen le Le Moal, 2011). Ka lebaka leo, ke habohlokoa ho ithuta likarolo tsa neurobiological tse amanang le ho fetoha ha motho ka bomong. Ho hlohlelletsa boitšoaro ke mokhoa oa liphoofolo o atisang ho sebelisoa ho batlisisa litšobotsi tsa neurobiological tsa ho lemalla lithethefatsi. Motheo oa mohlala ona ke hore liphello tse ikhethang tsa lithethefatsi li eketseha ha li ntse li pepeseha hangata. Hang ha e fumanoa, ho hlohlelletsoa ke mohaho ho nka nako e telele ebile ho na le kamano e tobileng ea nakoana le liphetoho tsa morphological and neurochemical ka tsela ea mesolimbic le li-nuclei tse 'maloa tse amanang le maikutlo le boitšoaro (Robinson le Kolb, 1999 'me Vanderschuren le Pierce, 2010). Thuto ea bopula-maliboho e tsamaisoang ke Masur le dos Santos (1988) ho bontšitse hore ho na le phapang e khōlō ea boitšoaro ho tsoa litlhapi tsa Swiss mabapi le ho hlohlelletsoa ha motlakase oa motlakase oa ethanol. Ho tloha ka nako eo lipatlisiso tse ling li bontšitse bohlokoa ba bohlokoa pakeng tsa lik'hemik'hale le mekhoa ea boitšoaro, haholo-holo tse amanang le dopaminergic (Abrahão et al., 2011, Abrahão et al., 2012 'me Souza-Formigoni et al., 1999) le mekhoa ea glutamatergic (Quadros et al., 2002a 'me Quadros et al., 2002b). Ho feta moo, thuto e fetileng ho laboratori ea rona e sebelisang podemedi ea tlhahiso ea motlakase ea ethanol e bontšitse hore litoeba tse hlokomelisitsoeng (empa e seng tse senisitsoeng) li hlahisitse keketseho e tsotehang ka mofuta oa kankere ea mofuta oa 1 (CB1R) nakong ea nako ea ho tlohela (Coelhoso et al., 2013). Mona re khethile mekhoa e fapaneng ea FosB / DeltaFosB polelo nakong ea ho tlohela pakeng tsa EtOH_High le EtOH_Low lihlopha.

Ho akaretsa, ho fapana ha boitšoaro bo boletsoeng molemong oa ho fumana mochine oa ethanol ho hlohlelletsoa ha lits'enyeho ho tsamaisana le polasetiki ea neuronal e khethollang nakong ea ho tlohela. Hoa thahasellisa hore liphello tsa rona li bontša hore mekhoa e fapaneng ea polelo ea FosB / DeltaFosB e fumanoa ka litoeba tse hlokomelisoang le tse sa utloisisoeng li amana haholo le nako ea ho tlohela ho e-na le ho ipeha kotsing ea lithethefatsi tse sa foleng, mohlomong ka lebaka la ho mamelloa ha phetolelo ea FosB / DeltaFosB e entsoeng ke lithethefatsi.

Tse latelang ke data e tlatsetsang e amanang le sehlooho sena.

References

• Nikulina et al., 2012
• EM Nikulina, MJ Lacagnina, S. Fanous, J. Wang, RP Hammer Jr.
• Ho senyeha ha maikutlo ho batho ka nako e sa lekanyetsoang ho ntlafatsa mesocorticolimbic ΔFosB / BDNF ho bonts'a maikutlo 'me ho phehella ho etsa hore li-neurons li sebetsane ka katleho le maikutlo a tsona: ho ameha ka ts'oaetso ea kelello ea psychostimulants
• Tsebo ea kelello, 212 (2012), maq. 38-48
• Sehlooho se

  |

   PDF (1552 K)

  |

  Sheba tlaleho ka Scopus

   | 

  Ho qotsa lihlooho (12)
•  
• Vialou et al., 2012
• V. Vialou, J. Feng, AJ Robison, SM Ku, D. Ferguson, KN Scobie, et al a.
• Sebopeho sa serame le karolo ea likarabo tsa cAMP tse tlama liprotheine li hlokahalang bakeng sa ho kenngoa ha cocaine ho ΔFosB
• J Neurosci, 32 (2012), maq. 7577-7584
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (17)
• Vanderschuren le Pierce, 2010
• LJ Vanderschuren, RC Pierce
• Mekhoa ea ho hlokomelisa lithethefatsi ho lemalla lithethefatsi
• Top Behav Neurosci ea Curr, 3 (2010), maq. 179-195
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (53)
• Vanderschuren le Kalivas, 2000
• LJ Vanderschuren, PW Kalivas
• Liphetoho ka phetisetso ea dopaminergic le glutamatergic ho kenngoa ha maikutlo le pontšo ea ts'ebeliso ea boitšoaro: tlhahlobo e boima ea lithuto tsa pele
• Psychopharmacology (Berl), 151 (2000), maq. 99-120
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (884)
• Swendsen le Le Moal, 2011
• J. Swendsen, M. Le Moal
• Motho e mong le e mong o kotsing ea ho lemala
• Ann NY Acad Sci, 1216 (2011), maq. 73-85
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (35)
• Souza-Formigoni et al., 1999
• ML Souza-Formigoni, EM De Lucca, DC Boipheliso, SC Enns, MG Oliveira, JN Nobrega
• Sensitization ho ethanol ea phello e tsotehang e amahanngoa le keketseho ea sebakeng sa bokhoni bo botle ba D2 receptor e tlamang
• Psychopharmacology, 146 (1999), maq. 262-267
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (54)
• Solecki et al., 2008
• W. Solecki, T. Krowka, J. Kubik, L. Kaczmarek, R. Przewlocki
• Karolo ea fosB ka boitšoaro bo amanang le moputso oa morphine le mohopolo oa sebaka
• Behav Brain Res, 190 (2008), maq. 212-217
• Sehlooho se

  |

   PDF (328 K)

  |

  Sheba tlaleho ka Scopus

   | 

  Ho qotsa lihlooho (7)
• Sim-Selley et al., 2011
• LJ Sim-Selley, MP ea Cassidy, A. Sparta, V. Zachariou, EJ Nestler, DE Selley
• Phello ea ΔFosB ho tlōla tekano ka ho bonts'oa ha li-opioid le cannabinoid-receptor mediated in the nucleus accumbens
• Neuropharmacology, 61 (2011), maq. 1470-1476
• Sehlooho se

  |

   PDF (446 K)

  |

  Sheba tlaleho ka Scopus

   | 

  Ho qotsa lihlooho (10)
• Ryabinin le Wang, 1998
• AE Ryabinin, YM Wang
• Tsamaiso e phetoang ea joala e ama ka mokhoa o fapaneng c-Fos le FosB protheine ea ho itšireletsa mafung ho DBA / 2 J litoeba
• Alcohol Clinic Exp Res, 22 (1998), maq. 1646-1654
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (33)
• Rodd-Henricks le al., 2000
• ZA Rodd-Henricks, DL McKinzie, RS Crile, JM Murphy, WJ McBride
• Sebaka se ikemetseng sa sebaka sa ho itšehla thajana ea ethanol ka har'a karolo ea ventral tegmental ea liphoofolo tsa basali tsa Wistar
• Psychopharmacology (Berl), 149 (2000), maq. 217-224
• Sheba tlaleho ka Scopus

  |

  Tlhaloso e feletseng ka CrossRef

   | 

  Ho qotsa lihlooho (130)
• Rodd et al., 2010
• ZA Rodd, RL Bell, SM Oster, JE Toalston, TJ Pommer, WJ McBride, et al a.
• Li-receptor tsa Serotonin-3 sebakeng sa morao-rao sa thibelo ea li-ventral li laola ethanol ho itlhomella joala-ho khetha (P) rats
• Joala, 44 (2010), maq. 245-255
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  Ho qotsa lihlooho (19)
• Rodd et al., 2004
• ZA Rodd, RI Melendez, RL Bell, KA Kuc, Y. Zhang, JM Murphy, et al a.
• Ho iketsetsa tsamaiso ea ethanol kahare ho ventral tegmental sebakeng sa banna ba malinyane: bopaki ba ho kenngoa ha dopamine neurons
• J Neurosci, 24 (2004), maq. 1050-1057
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  Ho qotsa lihlooho (111)
• Robinson le Kolb, 1999
• TE Robinson, B. Kolb
• Liphetoho tsa morpholoji ea li-dendrites le likhahla tsa dendritic nucleus accumbens le prefrontal cortex ka mor'a ho phekoloa khafetsa le amphetamine kapa k'hok'heine
• Eur J Neurosci, 11 (1999), maq. 1598-1604
• Sheba tlaleho ka Scopus

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  Ho qotsa lihlooho (427)
• Quadros et al., 2002b
• IM Quadros, JN Nóbrega, Hipolide ea DC, EM de Lucca, ML Souza-Formigoni
• Tsela e fapaneng ea ho etsa hore ethanol e matlafatse ha e amane le ho fetisetsoa ho li-receptor tsa D1 kapa tsa dopamine tsa bokooa ba mouse
• Addic Biol, 7 (2002), maq. 291-299
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  Ho qotsa lihlooho (21)
• Quadros et al., 2002a
• IM Quadros, Hip Hiplide, R. Frussa Filho, EM De Lucca, JN Nóbrega, ML Souza-Fomigoni
• Ho hanyetsa ethanol ho matlafatsa ho amahanngoa le ho eketseha ha mokhatlo oa NMDA ho kopanya libakeng tse itseng tsa boko
• Eur J Pharmacol, 442 (2002), maq. 55-61
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  Ho qotsa lihlooho (36)
• Phillips le al., 1997
• TJ Phillips, AJ Roberts, CN Lessov
• Ho ba le tšusumetso ea boitšoaro ho ethanol: liphatsa tsa lefutso le liphello tsa khatello ea kelello
• Pharmacol Biochem Behav, 57 (1997), maq. 487-493
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  Ho qotsa lihlooho (101)
• Perrotti et al., 2008
• LI Perrotti, RR Weaver, B. Robison, W. Renthal, I. Rent, S. Yazdani, et al a.
• Mekhoa e fapaneng ea DeltaFosB ho kenngoa ka bokooa bokong ka lithethefatsi tsa tlhekefetso
• Synapse, 62 (2008), maq. 358-369
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  Ho qotsa lihlooho (79)
• Perrotti et al., 2004
• LI Perrotti, Y. Hadeishi, PG Ulery, M. Barrot, L. Monteggia, RS Duman, et al a.
• Ho khahloa ke deltaFosB ka mekhoa ea boko bo amanang le moputso ka mor'a khatello ea maikutlo
• J Neurosci, 24 (2004), maq. 10594-10602
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  Ho qotsa lihlooho (148)
• Perrotti et al., 2005
• LI Perrotti, CA Bolaños, KH Choi, SJ Russo, S. Edwards, PG Ulery, et al a.
• DeltaFosB e bokella ka seleng ea GABAergic sepakapakeng ka mor'a mohatla oa postral tegmental sebakeng ka mor'a lefu la psychostimulant
• Eur J Neurosci, 21 (2005), maq. 2817-2824
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  Ho qotsa lihlooho (85)
• Ohnishi et al., 2011
• YN Ohnishi, YH Ohnishi, M. Hokama, H. Nomaru, K. Yamazaki, Y. Tominaga, et al a.
• FosB ke ea bohlokoa bakeng sa ho ntlafatsa mamello ea khatello ea kelello le ho hanyetsa ho matlafatsoa ke DFFB
• Biol Psychiatry, 70 (2011), maq. 487-495
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• Vialou et al., 2010
• V. Vialou, AJ Robison, QC Laplant, HE Covington III, DM Dietz, YN Ohnishi, et al a.
• DeltaFosB ka lipotolohong tsa moputso oa bokooa e kopana le botsitso ho khatello ea kelello le likarabo tse sithabetsang
• Nat Neurosci, 13 (2010), maq. 745-752
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  Ho qotsa lihlooho (141)
•  
• Zachariou et al., 2006
• V. Zachariou, CA Bolanos, DE Selley, D. Theobald, MP ea Cassidy, MB Kelz, et al a.
• Karolo ea bohlokoa bakeng sa DeltaFosB nucleus accumbens morphine khato
• Nat Neurosci, 9 (2006), maq. 205-211
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  Ho qotsa lihlooho (138)

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