Ho hlohlelletsoa ke lijo tse bakoang ke lijo, ho tšoaetsanoa ka sefapano ho cocaine le morphine, thibelo ea meriana, le phello ea ho ja lijo (2006)

J Neurosci. 2006 Jul 5;26(27):7163-71.

Le Merrer J1, Stephens DN.

PMID: 16822973

DOI: 10.1523 / JNEUROSCI.5345-05.2006

inahaneloang

Ts'ebetso e pheta-phetoang ea lithethefatsi tse hlekefelitsoeng e matlafatsa litlamorao tsa eona mme e fella ka tikoloho e nang le lithethefatsi e etsang hore ho be le maemo a itseng. Re lekile hore na lijo li baka litlamorao tse tšoanang. Litoeba tsa banna tse haelloang ke lijo li ile tsa fuoa lijo tse ncha nakong ea liteko tsa metsotso e 30 sehlopheng sa lifofane (sehlopha sa FR) se neng se lekanya tšebetso ea motlakase. Le ha tšebetso ea sehlopha sena e eketsehile ka ho lekoa khafetsa, ea sehlopha se pepeselitsoeng litselaneng tsa ho baleha empa se fumaneng lijo ka hokong ea lapeng (sehlopha sa FH), kapa sa sehlopha se khotsitsoeng ke prefeeding pele ho tlhahlobo (sehlopha sa SAT), se fokotsehile. Ha ba pepesetsoa litselaneng tsa ho baleha ha lijo li le sieo, sehlopha se kopaneng se ne se le mafolofolo ho feta lihlopha tse ling (ts'ebetso e hlophisitsoeng); ha ho na liphapang tsa ts'ebetso tse bonoeng sesebediswa se seng se seng se sa jang lijo. Ketsahalo e maemong e pholohile nako ea libeke tse 3 ntle le ho pepeseha ha mmila. Ketsahalo e hlophisitsoeng e ile ea fokotsoa ka mokhoa o ikhethileng ke mohanyetsi oa opiate naltrexone (10-20 mg / kg) le ke mohanyetsi ea sa amohelang tlholisano oa AMPA GYKI 52466 [1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-5H-2,3, 5-benzodiazepine hydrochloride] (10-1 mg / kg). Mohanyetsi oa D23390 SCH7 [R (+) - 8-chloro-3-hydroxy-1-methyl-2,3,4,5-phenyl-1-tetrahydro-3H-15-benzazepine hydrochloride] (30-2 microg / kg ) le D25 antagonist sulpiride (125-10 mg / kg) e fokolitse ts'ebetso e seng ka ho khetheha. Tekanyo e le 'ngoe ea "intraperitoneal" ea cocaine (20 mg / kg) kapa morphine (52466 mg / kg) e ekelitse ts'ebetso ha e bapisoa le letsoai, phello e matlafatsang e le kholo sehlopheng sa FR, e fana ka maikutlo a "ho hlohlelletsa maikutlo" ho lithethefatsi tsena. Leha ho le joalo, ho itlhahloba pele le GYKI XNUMX kapa naltrexone litekanyong tse neng li hatella tšebetso e nang le maemo liphoofolong tsa FR li ile tsa hatella ts'ehetso ea ts'oaetso ho cocaine. Ha e lumelloa lipapatso libitum phihlello ea lijo tseleng, litoeba tsa FR li jele li-pellets tse ngata tekong e lekantsoeng ka nako. Kahoo, likarolo tse ngata tsa ts'ehetso ea boits'oaro ho lithethefatsi li ka bonts'oa ho sebelisa moputso oa lijo mme li ka kenya letsoho ho ja haholo.

Selelekela

Ha e fuoa khafetsa, liphello tse susumetsang tsa lithethefatsi tsa tlhekefetso lia eketseha (Eikelboom le Stewart, 1982; Robinson le Becker, 1986). Ketsahalo ena e tsejoa e le ho hlohlelletsa boitšoaro 'me e ka ba nako e telele. Tlhekefetso bafuputsi ba hlahloba ts'oaetso ea boitšoaro e le mohlala oa polasetiki ea boitšoaro e amanang le tšebeliso e mpe ea lithethefatsi, ka tebello ea hore ho utloisisa mekhoa ea neural e thehiloeng ho mofuta ona oa polasetiki e ka fana ka tlhahisoleseding ka liketsahalo tse ling tsa polasetiki tse bakelang tlhekefetso. Khopolo e 'ngoe ea tšebeliso e mpe ea lithethefatsi le ho khutlela moraoRobinson le Berridge, 1993, 2001) ho ba le tšusumetso ea boitšoaro hobane hangata ho noa lithethefatsi ho matlafatsa phetisetso ea litsela tse nang le mekhoa e metle e atisang ho boloka mekhoa ea ho susumelletsa batho hore ba ts'oanele lithethefatsi le litakatso.

Likarolo tse ngata tsa ho hlohlelletsa boitšoaro li bonahala li bontša ho thehoa ha mekhatlo e hlophisitsoeng hantle pakeng tsa thepa e sa tsitsang ea lithethefatsi, le tikoloho eo lithethefatsi li nang le eona (Stewart et al., 1984; Vezina le Stewart, 1984; Stewart le Vezina, 1988; Vezina et al., 1989; Crombag le al., 1996), e le hore tikoloho eo lithethefatsi e 'nileng ea e-ba le eona e eketsa mosebetsi esita le ha ho se na lithethefatsi tse fanoang (mosebetsi o hlophisitsoeng) (Stewart, 1983). Ho totobetse hantle hore tšusumetso ea tikoloho e kopantsoeng le batho ba ka sehloohong ba nang le takatso ea lijo tse matlafatsang e ntlafatsa mosebetsi oa ho hohela (Sheffield le Campbell, 1954; Bindra, 1968). Hobane lithethefatsi tsa psychostimulant le opiate ke meputso e matla (Volkow le Bohlale, 2005), lits'ebeletso tsa tikoloho tse amanang le tsona li lokela ho eketsa mosebetsi. Ka lebaka leo, tlhaloso e ka 'nang ea hlalosoa ka liketsahalo tse bonts'itsoeng ke hore e bonahatsa kamano ea ho fana ka litekanyetso tsa tikoloho le lithethefatsi ho e-na le likamano tse tsosang takatso. Tabeng ena, moputso oa lithethefatsi o ne o ke ke oa lebelloa ho fapana le meputso ea tlhaho.

Tlaleho ena ea boemo bo tla ba e lumellanang le ho tšoana ho teng pakeng tsa boitšoaro bo botle le mefuta e meng ea thuto, le synaptic plasticity. Ka hona, ho fumana boipheliso ba boitšoaro bo thibetsoe ke mekhoa ea phekolo e akarelletsang bahanyetsi ba NMDA (Wolf le Khansa, 1991; Kalivas le Alesdatter, 1993; Stewart le Druhan, 1993) le protheine synthesis inhibitors (Karler et al., 1993) e thibelang menyetla ea nako e telele le thuto. Ho feta moo, hobane dopamine ke ketso ea eona ho D1 li-receptors li thusa polasetiki ea synaptic (Beninger le Miller, 1998; Nestler, 2001), keketseho ea psycho-stimulants e bakoang ke synaptic dopamine e ka thusa ho thehoa ha mekhatlo e ikemetseng e nang le maemo a matla pakeng tsa moferefere le tikoloho.

Sepheo sa thuto ea joale e ne e le ho hlahloba hore na lijo, moputso oa tlhaho, li ka tšehetsa ho khothaletsoa boitšoarong ho litoeba. Re ne re shebelletse mosebetsi oa ho lokisa litoeba tse haelloang ke lijo litseleng tseo ba neng ba pepesa ka tsona letsatsi le leng le le leng ho ea ho pelletsana e monate, 'me ba e bapisa le ea liphoofolo tse kenngoa letsatsi le leng le le leng ho ea ka litsela empa ha ho se na li-pellets (tse fanoeng hamorao lehaeng la lehae), kapa e pepesetsoeng ho pellets litseleng empa e satiated 30 min pele e lekoa. Tlhaloso ea mosebetsi o entsoeng ka boemo ba lijo e ile ea lekoa bakeng sa maemo a fapaneng le ho phela nako e telele, 'me ho kenngoa ha mekhoa ea dopaminergic, opioid, le AMPA glutamatergic e ile ea hlahlojoa. Ho khothaletsoa ho tšoaetsanoang ho matla ho liphello tse tsosang tsa cocaine le morphine li ile tsa lekoa, hammoho le liphello tsa naltrexone, 1- (4-aminophenyl) -4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), le R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) ho tšoaetsanoa ka sekhukhu ho cocaine. Qetellong, re ile ra hlahloba bokhoni ba lijo tse tsamaisanang le lijo ho etsa hore lijo tse eketsehileng tse ntseng li e-na le mefuta-futa li fumanehe.

Lisebelisoa le mekhoa

Lihlooho

Lihlooho e ne e le litoeba tsa banna (C57BL / 6 × SV129) tse hlahisitsoeng Lefapheng la Psychology Univesithing ea Sussex le ho lekola 25-30 g qalong ea liteko. Li ne li lula ka lihlopha tsa tse peli kapa tse tharo ka cage ka khantšo ea 12 h / khanya (e khantšang 7 PM), mocheso oa 19-21 ° C le 50% mongobo. Beke e le nngwe pele ho fumanoa ts'oaetso e bakoang ke lijo, litoeba e ne e le lijo feela tse fokotsang ho fokotsa litekanyo tsa 'mele ho ~ ~ xNUMX% ea boima ba tsona ba mahala. Metsi a ne a fumaneha ad libitum. Liteko tsohle li ile tsa amoheloa ke komiti ea melao ea boits'oaro 'me tsa etsoa tlas'a molao oa United Kingdom mabapi le liteko tsa liphoofolo [Molao oa Animal (Scientific Procedures), 1986].

Lisebelisoa tsa liteko

Mesebetsi ea ho itlhahisa hohle e ne e hlahlojoa ka li-polypropylene liphara tse chitja (bophara ba ka hare, cm 11; cm e ka ntle, 25 cm; bophahamo ba 25 cm) e nang le li-photobeamera tse robeli tse nonneng tse arohaneng ka nako e tloaelehileng 'Mead le Stephens, 1998). Palo ea ho phalla ha sefate ka mor'a likhetlo tse tharo tse latellanang tseleng e le 'ngoe e ne e sebelisoa e le tekanyo ea ts'ebetso ea pele. Boitsebiso bo nepahetseng bo ne bo lekoa ka lebokoseng la tšepe tse nang le mahlakore a mabeli [19 cm (bophara) × 45 cm (bolelele) × 20 cm (bophahamo)] e nang le maramo a mararo a sa tšoaneng a nang le mahlakore a mabeli a nang le lisekoere tsa 1 ka holim'a fatše 'me a arohane ka nako e telele ka nako e telele. Mosebetsi oa pele o ne o fumanoa ka makhetlo a mangata phoofolo e roba mela e 'meli e latellanang.

Hlahloba 1: ho fumana tlhahiso ea lijo tse nang le maemo a phomolo a lijo

Lenaneo ka leng le le leng la letsatsi le ne le e-na le preexposure run of 10 min (matha A), e lateloa ke khefu ea metsotso ea 5 nakong eo liphoofolo li ileng tsa nkeloa sebaka ka matlong a tsona a koaletsoeng malapeng. Joale litoeba li ne li khutlisetsoa litseleng tse tsamaeang ka maoto bakeng sa 20 min (matha B). Lenaneo lena le ne le etselitsoe ho etsisa mokhoa oa khale oa ts'ebeliso ea boitšoaro ho lithethefatsi, moo liphoofolo li kileng tsa tloaeloa ho koaletsoeng mesebetsing nakong ea pele, ebe li kenngoa ka lithethefatsi kapa koloi ea tsona ebe li khutlela litsing tsa liketsahalo bakeng sa boemo ba boemo bo matha.

Ho ile ha thehoa lihlopha tse tharo tsa liphoofolo tsa 10. Sehlopheng sa pele (lijo tse tsamaeang ka litsela, li lapile: FR), liphoofolo li ile tsa fuoa li-pellets tsa 20 tse nang le monate (20 mg mong le e mong; Noyes Precision pellets, Formule P; Lijo tsa Lipatlisiso, New Brunswick, NJ) ba qhalakaneng litseleng tseo ba li khutlelang bakeng sa ho matha B. Sehlopheng sa bobeli (lijo tsa lehae la malapa, ba lapile: FH), litoeba li ile tsa pepeseha litsela tse hlalositsoeng sehlopheng sa FR, ntle le hore ha se monate li-pellets li ne li fumaneha lisebelisoa. Li-pellets tse mashome a mabeli tse monate ka phoofolo li ne li fanoa ka kamoreng ea lehae 45 min ka mor'a bofelo ba nako ea boitšoaro. Sehlopha sa boraro (lijo tse tsamaeang le lipapali, satiated: SAT) e ne e le sehlopha sa FR, ho kenyeletsa le ho fumaneha ha pelletsane e monate, ntle le hore liphoofolo li ne li khaotsoe 30 pele ho nako ea ho itšoara ka ho amohela li-pellets tse tšoanang tse monate ad libitum malapeng a bona a lehae. Liphoofolo tsohle li ne li feptjoa ka li-laboratory tse tloaelehileng motšehare mantsiboea (3-4 PM) ka nako e fapaneng (60-90 min) kamora ho lekoa, ho fokotsa ho khoneha ho kopana pakeng tsa ho leka le ho fepa lijo. Liphoofolo li ne li sa tloaelehetsoe ke li-pellets pele li qala ho leka ho qoba ho kena-kenana le maemo a latelang. Liphoofolo tsa F li ne li ja li-pellets tsohle lipapaling ka mor'a lipapali tse peli ho isa ho tse tharo.

Hlahloba 2: moelelo oa moelelo oa karabo ea mokokotlo ea mokokotlo oa maemo a lijo

Qetellong ea mohato oa ho fumana chelete, liphoofolo tsa FR le lihlopha tsa FH li ne li pepesoa lipapaling kapa mabokose a mabeli a mosebetsi. Protocol e ne e tšoana le ea litekanyetso tsa ho fumana, ntle le hore mosebetsi oa pele o ne o lekanngoa ka ho ba sieo ha li-pellets tse natefalitsoeng (mosebetsi o hlophisitsoeng). Ka mor'a hore ba hlaphoheloe ka ho feletseng ts'ebetsong ea bona ea ts'ebetso (litekanyetso tse tharo ho isa ho tse 'nè tsa ho fumana lintho), liphoofolo li ile tsa khutlisetsoa morao ka taelo e fapaneng.

Lilemo tse telele tsa karabo ea mokokotlo ea maemo a nang le maemo a lijo

Ka morao ho likarolo tse tharo ho isa ho tse 'nè tsa ho fumana lihlahisoa, liphoofolo tsa FR le FH li ile tsa khutlisetsoa morao bakeng sa ts'ebetsong ea likoloi (letsatsi la 1). Ha hoa ka ha fuoa li-pellets tse monate. Lenaneo le latelang e ne e le lenaneo le tloaelehileng la ho fumana chelete, li-pellets tse monate li fumaneha. Joale mananeo a letsatsi le leng le le leng a emisoa bakeng sa libeke tsa 3, liphoofolo tse setseng tlas'a tlhompho ea lijo. Ka letsatsi la 22, litoeba li ile tsa boela tsa bonahala litseleng tse sa sebetseng ha ho se na li-pellets tse monate ho hlahloba liketsahalo tse tsamaisitsoeng hantle.

Hlahloba 3: liphello tsa bahanyetsi ba dopaminergic ha ho bontšoa ketsahalo e entsoeng ke lijo

Ho na le lihlopha tse peli tsa liphoofolo tse sa nahaneng tsa 9-10 (sehlopha sa FR le FH). Qetellong ea mohato oa ho fumana, liphoofolo tsena li ne li kenngoa le D1 mohanyetsi oa batho ba amohelehang SCH23390 (ka 15 kapa 30 μg / kg, ip) kapa koloi ho latela seqapi sa Latin square; ha hoa ka ha fanoa ka li-pellets tse monate. Liphoofolo li ne li kenngoa 5 min pele ho matha A, ho hlahloba liphello tse ka hlahisoang ke mosebetsi o lebeletsoeng. Ka mor'a thuto ea liteko tsa lithethefatsi, liphoofolo li ne li kenngoa mananeong a mararo a mane a tloaelehileng a ho fumana (li-pellets tse monate tse fumanehang) ho lumella ho hlaphoheloa ka botlalo ha boemo ba bona bo sebetsang. Tse ling tse peli FR le FH (n = Li-7-9) lihlopha li entsoe ho tsoa liphoofolong tse se nang boikemisetso ho leka liphello tsa D2/D3 sulpiride ea li-receptor (25, 75, kapa 125 mg / kg) khahlanong le koloi, ho sebelisa moqapi o le mong oa liteko, ntle le hore sulpiride e kenngoa 30 min pele ho matha A.

Hlahloba 4: liphello tsa li-opiate le li-AMPA tse amohelang batho ba nang le maikutlo a phofshoang ke lijo

Likokoana-hloko tsa FH le FR tse neng li lekoa ka nako e telele li ile tsa kenngoa ka katleho le mohanyetsi oa npilexete (10 le 20 mg / kg, ip) kapa koloi ea nonselective e sa feleng empa e le nako e telele ea nakoana le GYKI 52466 (5 kapa 10 mg / kg, ip) ) kapa koloi, ho latela sebopeho sa Latin square; ha ho na li-pellets tse monate tse neng li fumaneha nakong ea bonnete ba B. Naltrexone e neng e tsamaisoa 30 min pele ho matha A; GYKI 52466 e ne e kenngoa hang-hang pele e matha A ka lebaka la khutso ea eona e khutšoanyane. Ka mor'a thuto ea liteko tsa lithethefatsi, liphoofolo li ne li fanoa ka linako tse tharo ho isa ho tse 'nè tsa ho fumana lintho tse tloaelehileng ho lumella ho hlaphoheloa ka botlalo ha boemo ba bona bo sebetsang

Hlahloba 5: liphello tsa cocaine le morphine phephetso e entsoeng

Ho ile ha thehoa lihlopha tse peli tsa liphoofolo tse sa tšoaneng tsa 10: sehlopha sa FR le sehlopha sa FH. Qetellong ea mohato oa ho fumana chelete, liphoofolo li amohetse phephetso e entsoeng ka cocaine (10 mg / kg, ip) kapa ente ea saline (hang-in) pele e matha B; ha hoa ka ha fanoa ka li-pellets tse monate. Ho matha B ho mpa feela ho na le 10 min. Ka mor'a hore ba hlaphoheloe ka botlalo boemo ba bona ba tshebetso (mananeo a mararo ho isa ho a mane), liphoofolo li ile tsa khutlisetsoa morao ka tatellano. Ka tsela e tsoanang, lihlopha tse ling tse peli tsa tse robeli tse robeli le tse robeli tsa motlakase li ile tsa etsoa ho leka liteko tsa morphine ts'oaetso ea phephetso. Qetellong ea mohato oa ho fumana lintho, liphoofolo li amohetse morphine (20 mg / kg, ip) kapa sejoe sa saline (15 min pele ho matha A; ha hoa ka ha fanoa ka li-pellets tse monate. Ho matha B ho ile ha nka metsotso ea 10. Ka mor'a hore ba hlaphoheloe ka ho feletseng ka boemo ba bona ba ts'ebetso, liphoofolo li ile tsa khutlisetsoa morao ka tatellano e fapaneng.

Ho feto-fetoha ha liphello tsa cocaine ka AMPA, opiate, kapa dopamine D1 bahanyetsi ba amohelang

Liphoofolo tsa FR le FH tse neng li kile tsa tšoaroa ka naltrexone le GYKI 52466 li ile tsa sebelisoa tekong ena. Ka morao ho likarolo tse tharo ho isa ho tse 'nè tsa ho fumana chelete, ba ile ba amohela GYKI 52466 (10 mg / kg, ip) pele ho matha A e lateloa ke cocaine (10 mg / kg, ip) pele ho matha B, kapa koloi (saline) pele ho matha A e lateloa ke cocaine pele matha B; ha hoa ka ha fanoa ka li-pellets tse monate. Ka mor'a hore ba hlaphoheloe ka ho feletseng ka boemo ba bona ba ts'ebetso, liphoofolo li ile tsa khutlisetsoa morao ka tatellano e fapaneng. Eaba ba khutlisetsoa maemong a tšoanang, empa ba fumana naltrexone (20 mg / kg) kapa SCH23390 (30 μg / kg) ho e-na le GYKI 52466. GYKI 52466 le SCH23390 li ne li kenngoa hang-hang pele li matha A, 'me naltrexone e ne e tsamaisoa ka 30 min pele ho matha A.

Hlahloba 6: bokhoni ba tikoloho e tsamaeang ka lijo ho ntlafatsa lijo

Liphoofolo tsa FR le FH tse neng li phekoloa pele ka sulpiride li ile tsa lekoa maemong a liteko a tšoanang le nakong ea litheko, ntle le hore matha B a ne a nka 5 min feela le hore li-pellets tse 80 tse tsoekere li ne li le teng ka nako eo. Ketsahalo ea kantle e ne e beiloe leihlo nakong ea ho matha A le ho matha B. Palo ea li-pellets tse fumanehang bakeng sa toeba ka 'ngoe e ile ea lekanngoa pele le kamora ho matha B (ho nahanoa ka tšollo ea letho). Ho ja lijo ka toeba e 'ngoe le e' ngoe ho hlahisitsoe ka ligrama kapa ke karolo ea boima ba 'mele ba phoofolo.

lithethefatsi

Cocaine hydrochloride, SCH23390, naltrexone (Sigma, Poole, UK), le morphine hydrochloride (McFarland Smith, Edinburgh, UK) li ile tsa qhibiliha ka 0.9% saline e bolileng 'me ea kenngoa intraperitoneally ka molumo oa 10 ml / kg. (±) Sulpiride (Tocris, Avonmouth, UK) hammoho le mohanyetsi oa AMPA, GYKI 52466 (IDR, Budapest, Hungary) e ile ea qhibiliha ka molumo o monyenyane oa hydrochloric acid (0.1 m), e hloekisitsoeng ka sephahla 0.9% saline ho fihlela ho hopola e tlisitsoe pH 6.5-7 le NaOH (1 m).

Lipatlisiso tsa sethathamo

Leka 1.

Lintlha li ile tsa hlahlojoa ka li-ANOVAs tse peli ka sehlopha (FR, FH, SAT) e le pakeng tsa-sehlooho se itseng, le seboka e le se ka hare-taba. Ha tšusumetso ea bohlokoa e fumanehang, post hoc tlhahlobo e entsoe ka ho sebelisa teko ea Seithuti-Newman-Keuls. Ka tsela e le 'ngoe, BAOVA ba na le lihlopha tse lekanang le sehlopha se seng le se seng ho hlahloba liphetoho liketsahalong tsa mosebetsi.

Leka 2.

Liphapang tsa ts'ebetso ea locomotor lipakeng tsa lihlopha tsa FR le FH maemong a fapaneng li ile tsa hlahlojoa ho sebelisoa tsa Baithuti t tlhahlobo bakeng sa mehlala e ikemetseng. Mabapi le teko ea nako e telele, lintlha li ile tsa hlahlojoa ka li-ANOVAs tse peli ka sehlopha e le pakeng tsa-taba le letsatsi (1 kapa 22) e le tekanyo e pheta-phetoang.

Liteko tsa 3 le 4.

Lintlha tse mabapi le maemo a fapaneng a kalafo li ile tsa hlahlojoa ka li-ANOVAs tse peli ka sehlopha (FR, FH) e le pakeng tsa-taba, le tekanyo e lekanngoe ka makhetlo a mangata. Ka tsela e le 'ngoe TSEO e nang le sebopeho e le sebopeho se ka hare-hare se ne se sebelisetsoa ho hlahloba liphetoho tse itšetlehileng ka tekanyo ea likhahla mosebetsing.

Leka 5.

Ditaba tsa mefuta e fapaneng ea phekolo e ne e hlahlojoa ka li-ANOVA tse peli ka sehlopha (FR, FH) e le pakeng tsa-taba, le kalafo kapa ho iketselletsa pele ho feta tekanyo e phetoang.

Leka 6.

Liphapang tsa ho ja lijo lipakeng tsa lihlopha tsa FR le FH maemong a fapaneng li ile tsa hlahlojoa ho sebelisoa seithuti t tlhahlobo bakeng sa mehlala e ikemetseng.

Results

Leka 1

Litoeba li ne li lumelloa hore li hlahlobe litsela tse chitja tsa 10 min (matha A) pele li tlosoa ka bokhutšoanyane ho lumella li-pellets tse monate li behoa tseleng, ebe li khutlisetsoa (li matha B). Joalokaha ho bontšitsoe ho Setšoantšo sa 1A, ts'ebetsong ea letsatsi le leng le le leng ho ts'oanelang lijo lipapaling ka nako ea B ka lipampiri tsa 14 e lebisitseng ts'ebetsong e phahameng ea mosebetsi oa boipheliso nakong ea A (ts'ebetso e lebellang) sehlopheng se amohetseng lijo tseleng ha li lapile (sehlopha sa FR), empa eseng ka litoeba tse ileng tsa fumana lijo ka lekholong la ntlo (FH) kapa litoeba tse neng li feptjoa ka ho fepa pele li behoa tseleng (SAT) (sehlopha sa phello: F(2,26) = 6.53, p <0.01; Phello ea linako: F(13,338) = 3.39, p <0.0001). Nakong ea liboka tse 14, tšebetso e ne e phahame sehlopheng sa FR ho feta lihlopheng ka bobeli tsa FH le SAT (post hoc, p <0.01), e bakoang ke ho fokotseha ho hoholo ha tšebetso nakong ea liboka tsa FH (F(13,117) = 2.93; p <0.01) le SAT (F(13,104) = 2.15; p <0.05), empa eseng sehlopheng sa FR (F(13,117) = 1.37; NS).

 

Setšoantšo sa 1. 

Ho fumanoa ha mesebetsi e entsoeng ka lijo. Ho ts'oaroa letsatsi le leng le le leng (li-sessions tsa 14) ho li-runway tse tsamaisoang ke lits'ebeletso ho entse hore ho etsoe mosebetsi o eketsehileng (ho bolela ± SEM) ka nako ea A (A) le ho matha B (B) liphoofolong tse lapileng tse fumanoang li-pellets tse monate (FR) (n = 10) ha e bapisoa le liphoofolo tse lapileng tse fumanoang li-pellets tse monate matlong a bona a lehae (FH) (n = 10) le liphoofolo tse nang le li-pellets tse monate tse fumanehang ad libitum 30 min pele ho teko (SAT) (n = 10). Ho abela mosebetsi ona ho na le likhapa tsa 5 min ka mananeo a mabeli a ho qetela (ho bolela ± SEM) ho bontšitse hore mosebetsi oa boipheliso o eketsehile qetellong ea phallo B ho liphoofolo tsa FH hangata li pepesehetse litseleng (C), ho loka bakeng sa tlhahlobo e fapaneng ea 5 ea pele ea metsotsoana ea B (D) (*p <0.05; ∗∗p <0.01, ANOVA e lateloa ke Newman-Keuls post hoc tlhahlobo).

 

Ka tsela e ts'oanang, ho fana ka mapolanka a monate litseleng tsena ho boetse ho fella ka ho eketseha ha mosebetsi oa motlakase nakong ea B ea sehlopha sa FR, athe mosebetsi o fokotsehile ka lihlopha tsa FH le tsa SAT (sehlopha sa ts'ebetso: F(2,26) = 8.00, p <0.01; Phello ea linako: F(13,338) = 3.53, p <0.0001; Tšebelisano ea G × S: F(26,338) = 3.99, p <0.0001) (Feie. 1B). Nakong ea koetliso, mosebetsi o ne o phahame sehlopheng sa FR ho feta lihlopha tse peli tsa FH le tsa SAT (post hoc bohlokoa ho feta sehlopha sa FH: p <0.05; vs sehlopha sa SAT: p <0.01), e bonts'a keketseho e kholo ho pholletsa le linako sehlopheng sa FR (F(13,117) = 3.12; p <0.001), tseo bongata ba tsona li etsahalang kamora mananeo a mararo ho isa ho a mahlano, empa ho fokotseha ha FH (F(13,117) = 6.21; p <0.0001) le SAT (F(13,104) = 3.70; p <0.0001) lihlopha.

Nako ea nako ea ho lokisa mosebetsi nakong ea B ea lihlahisoa ka makhetlo a mangata a pepesetsoeng litseleng e ile ea hlahlojoa ka ho bontša mosebetsi oa litšebeletso tsa lichelete tsa 5 min ka mananeo a mane a ho qetela (11-14) (Feie. 1C). Ketsahalo e ne e phahame ho liphoofolo tsa F ho feta liphoofolo tsa FH le tsa SAT (phello ea sehlopha: F(2,26) = 7.29; p <0.01), ka tloaelo e akaretsang ea ho eketseha ha pheletso e qala (phello ea nako: F(2,26) = 7.01; p <0.001). Leha ho le joalo, tloaelo e joalo e fihlelletse bohlokoa liphoofolong tsa FH feela (F(3,27) = 5.25; p <0.01), eseng ho FR (F(3,27) = 2.61; NS) kapa liphoofolo tsa SAT (F(3,27) = 1.23; NS). Phapang e ikhethang ka ho fetisisa pakeng tsa FR le FH / SAT lihlopha li ile tsa bonoa nakong ea pele ea 5 ea B ea B (F(2,26) = 10.28; p <0.0001), leha ho na le nako e hlokoang ke liphoofolo tsa FR ho ja li-pellets tsa tsoekere (li-pellets tsohle li ne li jeoa ka ∼3-4 min). Ha re nahana ka sephetho sena, re fokolitse tlhaiso-leseling ea lipalo ho data ho tloha metsotsong ea pele ea 5 ea run B (Feie. 1D). Liphoofolo tsa F, empa ha li liphoofolo tsa FH kapa SAT, li hlahisitsoe keketseho e kholo mosebetsing oa tsona oa lihlahisoa likopanong tsa 14 (boholo ba keketseho bo hlahang mananeong a mararo ho isa ho a mane) ha li-pellets tse monate li fumaneha nakong ea B (phello ea sehlopha: F(2,26) = 8.52, p <0.01; Phello ea linako: F(13,338) = 5.95, p <0.0001; Tšebelisano ea G × S: F(26,338) = 3.80, p <0.0001). Hape, ts'ebetso e ne e phahame ho feta linako tse 14 sehlopheng sa FR ho feta lihlopheng tsa FH le SAT (post hoc bohlokoa, p <0.01). ANOVA e latelang e bontšitse keketseho e kholo ea ts'ebetso sehlopheng sa FR nakong ea liboka (F(13,117) = 4.80; p <0.0001) empa phokotso e kholo ea FH (F(13,117) = 4.86; p <0.0001) le SAT (F(13,104) = 4.07; p <0.0001) lihlopha.

Leka 2

Ha li lekoa litseleng tse chitja ha ho se na li-pellets tse monate, liphoofolo tse tsoang ho sehlopha sa FR li ne li le mafolofolo ho feta liphoofolo tsa FH nakong ea phallo A (t(18) = 2.72, p <0.05; mosebetsi ± SEM: FH, 33.90 ± 5.84; FR, 80.60 ± 16.25), nakong ea ho matha B (t(18) = 3.39, p <0.01; ketsahalo ± SEM: FH, 28.10 ± 13.86; FR, 152.60 ± 34.02), mme, haholo-holo, nakong ea metsotso e 5 ea pele ea run B (t(18) = 4.02; p <0.01) (Feie. 2A). Ha ho etsoa liteko tse fapaneng (li-mabokose a mabeli a maiketsetso a li-rectangular) tse sa kang tsa e-ba le lijo, 'me ho se na li-pellets tse monate, li-FR li ne li sa fapane le liphoofolo tsa FH nakong ea mosebetsi oa pele nakong ea A (t(18) <1.63, NS; ketsahalo ± SEM: FH, 24.10 ± 4.25; FR, 44.80 ± 11.77), matha B (t(18) = 1.48, NS; ketsahalo ± SEM: FH, 39.30 ± 8.74; FR, 72.70 ± 20.87) kapa nakong ea pele ea 5 ea metsotsoana ea B (t(18) = 1.34, NS) (Feie. 2A).

 

Setšoantšo sa 2. 

Boitsebiso bo nepahetseng le nako e telele ea mosebetsi o entsoeng ke lijo (ho bolela + SEM). Ha e lekoa litsing tse ling ha ho se na li-pellets tse monate, liphoofolo li fanoa ka lipuo tse natefetsoeng tse natefetsoeng ka mokhoa ona (FR) (n = 10) e bonahatsa mesebetsi e phahameng ho feta liphoofolo tse fuoeng pellets malapeng a bona a lehae (FH) (n = 10), nakong ea pele ea 5 ea metsotso ea B (A, ho tloha) (*p <0.05, ∗∗p <0.01, Seithuti t tlhahlobo). Ha e lekoa ka taba e fapaneng (A, ka ho le letona), liphoofolo tsa F ha lia ka tsa sebetsa haholo ho feta liphoofolo tsa FH. Hlokomela hore litekanyo li fapane. Phapang ea ketsahalo e pakeng tsa FR (n = 9) le FH (n = 10) liphoofolo ha li ntse li matha ka letsatsi 1 (D1) e phethile libeke tse ling tsa 3 [ho fihlela letsatsing la 22 (D22) ea ho sitisa ho shebana le lisebelisoa tsa letsatsi le leng le le leng (B) (*p <0.05; ∗∗p <0.01, Seithuti t tlhahlobo).

 

Ha thupelo ea litsela e emisoa libeke tsa 3, keketseho ea mosebetsi oa ho lokisa nakong ea A le ho matha B e ne e hlokomeloa lihlopha ka bobeli tsa liphoofolo, empa liphoofolo tsa F li ile tsa tsoela pele ho sebetsa haholo ho feta liphoofolo tsa FH (mosebetsi ± SEM: matha A, letsatsi la 1, FH, 43.10 ± 7.98; 80.11 ± 13.08; X, 22 ± 64.10; B, letsatsi 12.93, FH, 156.00 ± 39.74; 1 ± 39.10; 13.34, FH, 170.67 ± 43.26; FR, 22 ± 110.40). Litsela tse peli tsa ANOVA ka letsatsi le sehlopha sa ho hlahloba ha lintlha li senola bohlokoa bo boholo ba sehlopha (F(1,17) = 6.61, p <0.05; F(1,17) = 5.67, p <0.05, ka ho latellana) le letsatsi la liteko (F(1,17) = 8.28, p <0.05; F(1,17) = 8.02, p <0.05, ka ho latellana) ntle le tšebelisano e kholo. Ka lehlakoreng le leng, tšitiso e ne e se na tšusumetso e kholo mesebetsing nakong ea metsotso e 5 ea pele ea B, liphoofolo tsa FR li lula li le mafolofolo ho feta liphoofolo tsa FH (sehlopha: F(1,17) = 8.19, p <0.05; letsatsi le lekang phello: F(1,17) = 2.17, NS) (Feie. 2B).

Leka 3

Ho iketelletsa pele le SCH23390 e ne e se na phello mosebetsing oa motlakase nakong ea A (phello ea sehlopha: F(1,17) = 0.90, NS; ho sebetsa ha tekanyo: F(2,34) = 0.86, NS). Liphoofolo tsa F li ne li le mafolofolo ho feta liphoofolo tsa FH ha li ntse li matha B (phello ea sehlopha: F(1,17) = 5.17, p <0.05), mohlala o neng o sa fetoloa ke SCH23390 liente (phello ea lethal: F(2,34) = 2.06, NS) (Lethathamo 1). Sena se ne se bakoa ke ho se be teng ha SCH23390 e sebetsa sehlopheng sa FR (F(2,16) = 0.32; NS), athe ho fokotseha ha mosebetsi ho ile ha hlokomeloa ho sehlopha sa FH (F(2,18) = 6.20; p <0.01). Ho tsepamisa maikutlo ho metsotso e 5 ea pele ea B (Feie. 3A), Liphoofolo tsa F li ne li boetse li sebetsa ho feta liphoofolo tsa FH le SCH23390 liente li hlōlehile ho thibela phapang ena (phello ea sehlopha: F(1,17) = 16.51, p <0.001), leha e le maemong a phahameng ka ho fetisisa e neng e tloaetse ho fokotsa ts'ebetso ea locomotor (phello ea tekanyetso: F(2,34) = 3.60, p <0.05). Phello ena, leha ho le joalo, ha ea ka ea fihlela bohlokoa ho FR (F(2,16) = 2.11; NS) kapa FH (F(2,16) = 2.65; NS) sehlopha.

 

Tafole 1. 

Liphello tsa SCH23390, sulpiride, naltrexone le GYKI 52466 mesebetsing e entsoeng ke lijo (e bolela ± SEM) e lekantsoeng nakong ea phallo A le ho matha B (20 min)

 

 

Setšoantšo sa 3. 

Liphello tsa SCH23390 (A), sulpiride (B), naltrexone (C), le GYKI 52466 (D) ho etsa lintho tse entsoeng ka lijo (ho bolela ± SEM). SCH23390 'me sulpiride e ile ea hlōleha ho thibela likarabo tsa lijo nakong ea pele ea 5 ea metsotso ea B liphoofolong tse neng li kile tsa pepesoa mapolanka a monate litseleng (FR) (n = 9 ka lithethefatsi) ha ho bapisoa le liphoofolo tse fumanoang li-pellets tsa lehae lelapeng la tsona (FH) (n = 7-10 ka lithethefatsi). Ka lehlakoreng le leng, ho tsuba ha lijo ho bakoang ke lijo ho ile ha thibeloa ka morao ho latela naltrexone kapa GYKI 52466 pele ho phekolo ka liphoofolo tsa F (n = 8-9 ka lithethefatsi), ka tekanyo ea (20 le 10 mg / kg, ka ho latellana) e neng e se na phello mesebetsing ea basal liphoofolong tsa FH (n = 10 ka lithethefatsi) (*p <0.05, ∗∗p <0.01, Seithuti t teko ho bapisa lihlopha tsa FH le FR bakeng sa tekanyo e 'ngoe le e' ngoe).

 

Le hoja ho eketseha ha tekanyo ea sulpiride ho fokotsoe ts'ebetso ho litoeba tsohle nakong ea matha A, liphoofolo tsa FR li ile tsa lula li sebetsa ho feta liphoofolo tsa FH (sehlopha sa phello: F(1,14) = 6.02, p <0.05; phello ea tekanyo: F(3,42) = 8.32, p <0.01). Ka mokhoa o ts'oanang, liphoofolo tsa FR li bonts'itse tšebetso e phahameng ea locomotor nakong ea ho matha B (sephetho sa sehlopha: F(1,14) = 11.72, p <0.01), le kalafo ea pele ho pelo ea sulpiride, leha e fokotsa ts'ebetso ka tekanyetso e eketsehang, e ne e sena phello e kholo phapang ena (phello ea tekanyetso: F(3,42) = 4.67, p <0.01) (Lethathamo 1). Qetellong, nakong ea pele ea 5 ea ho matha B feela, litoeba tsa FR li ne li le mafolofolo ho feta likhohlo tsa FH (sehlopha sa phello: F(1,14) = 7.65, p <0.05), 'me sulpiride e fokolitse tšebetso ea li-locomotor ka tsela e ts'oanang lihlopheng ka bobeli (phello ea tekanyetso: F(3,42) = 4.86, p <0.01) (Feie. 3B).

Leka 4

Naltrexone pele ho ts'oaetso e fokotsitse mosebetsi oa ho etsa mosebetsi nakong ea A, liphoofolo tsa F li hlōleha ho ba mafolofolo haholo ho feta liphoofolo tsa FH (sehlopha sa phello: F(1,16) = 2.02, NS; ho sebetsa ha tekanyo: F(2,32) = 6.82, p <0.01). Ka lehlakoreng le leng, liphoofolo tsa FR li bonts'itse ts'ebetso e phahameng ho feta liphoofolo tsa FH nakong ea ho matha B (sehlopha: F(1,16) = 7.58, p <0.05), phapang eo naltrexone e neng e tloaetse ho e hatella (phello ea tekanyetso: F(2,32) = 1.72, NS) (Lethathamo 1). Joalokaha ho bontšitsoe ho Setšoantšo sa 3C, Liphoofolo tsa F e ne e le mafolofolo ho feta liphoofolo tsa FH nakong ea pele ea 5 ea metsotsoana ea B (sehlopha sa phello: F(1,16) = 11.36, p <0.01). Naltrexone ka ho khetheha e fokolitse tšebetso e nang le maemo liphoofolong tsa FR, ntle le ho ama ts'ebetso ea locomotor liphoofolong tsa FH (phello ea tekanyetso: F(2,32) = 5.74, p <0.05; Tšebelisano ea G × D: F(2,32) = 6.09, p = 0.01). Ka tsela e 'ngoe, ANOVA e bontšitse ho fokotseha ha tekanyo ea tekanyo ea likhahla ka liphoofolo tsa F (F(2,14) = 6.11; p <0.05) empa ha ho na phello liphoofolong tsa FH (F(2,18) = 0.90; NS).

Kalafo le mohanyetsi oa AMPA, GYKI 52466, e ne e atisa ho fokotsa mosebetsi oa ho lokisa lihlopha ka bobeli nakong ea phallo A (phello ea lethal: F(2,34) = 3.02, NS), FR le liphoofolo tsa FH tse nang le maemo a tšoanang (sehlopha sa phello: F(1,17) = 1.37, NS). GYKI 52466 e ile ea fokotsa mosebetsi oa lihlahisoa lihlopheng tsena ka bobeli nakong ea phallo ea B, empa ho fokotseha hona ho ne ho tsebahala haholoanyane ka FR ho feta liphoofolong tsa FH (sehlopha sa phello: F(1,17) = 4.06, NS; ho sebetsa ha tekanyo: F(2,34) = 9.10, p <0.001; Tšebelisano ea G × D: F(2,34) = 3.73, p <0.05) (Lethathamo 1). Lijo tsa GYKI 52466 tse fokotsoang ka ho khetheha li sebetsane le liphoofolo tsa FF nakong ea pele ea 5 ea metsotsoana ea B (Feie. 3D), ntle le ho fetola mosebetsi oa lihlahisoa ho liphoofolo tsa FH (sehlopha sa phello: F(1,17) = 5.23, p <0.05; phello ea tekanyo: F(2,34) = 10.30, p <0.001; Tšebelisano ea G × D: F(2,34) = 6.43, p <0.01). ANOVA e latelang e bontšitse phello e kholo ea GYKI 52466 liphoofolong tsa FR (F(2,16) = 8.73; p <0.01) empa ha ho na phello liphoofolong tsa FH (F(2,16) = 1.38; NS).

Leka 5

E le ho hlahloba hore na ho khothaletsa boitšoaro hoa lijo ho bonts'itse ho tšoaetsanoa ha cocaine, re kentse cocaine hang-hang pele re matha B (Feie. 4A). Ka mor'a hore e entsoe ka saline le ha ho se na li-pellets tse monate, liphoofolo tse tsoang sehlopha sa FR li bontšitse ho eketseha ha mosebetsi nakong ea B (10 min) e amanang le likhoho tsa FH (boemo bo hlophisitsoeng; t(18) = 2.15, p <0.05); ente ea ts'ebetso e ntlafalitsoeng ea k'hok'heine, ha e bapisoa le ente ea letsoai, lihlopheng ka bobeli, empa keketseho ea tšebetso kamora k'hok'heine e ne e phahame ho FR ho feta sehlopha sa FH. ANOVA ea litsela tse peli le sehlopha (G) le lithethefatsi (D) e le lintlha tse senolang phello e kholo ea sehlopha (F(1,18) = 9.46; p <0.01) le kalafo ea lithethefatsi (F(1,18) = 23.90; p <0.001), ka tšebelisano ea bohlokoa ea G × D (F(1,18) = 6.18; p <0.05).

 

Setšoantšo sa 4. 

Liphello tsa phephetso ea cocaine (A) kapa morphine (B) ente ea karabo e entsoeng ka lijo (mokhoa + SEM). Cocaine e ne e kenngoa hang-hang pele e matha B; morphine e ne e fanoa ka 15 min pele ho matha A. Cocaine le morphine li ile tsa eketsa mesebetsi ea liphoofolo liphoofolong tsohle; leha ho le joalo, phello ea bona e tsosang takatso e ne e ka hlahisa liphoofolo tse nang le lijo tse nang le lijo (FR) (n = 8-10), ha e bapisoa le litaelo (FH) (n = 8-10). Liphello tsa ho nkeloa pele ke GYKI 52466 (C), naltrexone (D), kapa SCH23390 (E) ho tšoaetsanoa ka sekhukhu ho cocaine. GYKI 52466 e kenngoa hang-hang pele e matha A kapa naltrexone e entsoeng ka 30 min pele ho matha A thibelitsoe ho tšoaetsanoa ho tšoaetsanoang ha cocaine liphoofolong tsa FR (n = 9), mme mosebetsi o ne o sa fapane le liphoofolo tsa FH (n = 7). SCH23390 e fokotsitse liphello tse hlasimollang tsa cocaine empa ea hlōleha ho thibela phapang pakeng tsa FR le liphoofolo tsa FH (*p <0.05, ∗∗p <0.01, Seithuti t teko ho bapisa lihlopha tsa FR le FH ka boemo bo bong le bo bong; †p <0.05, ††p <0.01, †††p <0.001, ANOVA).

 

Ho fokotsa sefahleho ho morphine ho ile ha hlahlojoa ka ho kenya morphine 15 min pele ho matha A (Feie. 4B). Mosebetsi oa pele o ile oa eketseha ka ho itšireletsa ka morphine ka FR le liphoofolo tsa FH nakong ea phallo A (phello ea lithethefatsi: F(1,14) = 10.93, p <0.01), ho se na phapang lipakeng tsa lihlopha (sephetho sa sehlopha: F(1,14) = 0.11, NS; saline FH, 62.62 ± 16.49; FR, 87.50 ± 25.98; morphine FH, 210.62 ± 40.10; FR, 219.50 ± 80.34). Ha nako ea B e ntse e sebetsa, phephetso ea morphine e ntlafatsoa mosebetsing lihlopheng tsena ka bobeli ha li bapisoa le saline (phello ea lithethefatsi: F(1,14) = 5.10, p <0.05), mme ts'ebetso e ile ea lula e phahame ho liphoofolo tsa FR ho feta liphoofolong tsa FH (phello ea sehlopha: F(1,14) = 21.55, p <0.001).

Ho kenya letsoho mosebetsing oa ho ja lijo ka lebaka la ho tšoaetsanoa ha li-cocaine ho ile ha hlahlojoa ka ho etsa liphoofolo pele ho GYKI 52466 le naltrexone, ka litekanyetso tse bontšitsoeng ho thibela liketso tsa boemo bo hlakileng litsing tse fetileng, kapa SCH23390, e leng, esita le ka tekanyo e fokotsang mosebetsi oa lefats'e lohle, e sa khone ho thibela mosebetsi o hlophisitsoeng. Ho qaqisoa ha koloi kapa GYKI 52466 ha ho na phello mosebetsing nakong ea lipapali tsa A, liphoofolo tsa F tse hlōlehang ho sebetsa ka nako e telele ka nako eo liphoofolo tsa FH (tlhahiso ea ho itšireletsa pele: F(1,16) = 0.23, NS; phello ea sehlopha: F(1,16) = 0.23, NS; ketsahalo ± SEM: FH saline, 38.20 ± 11.01; FR, 63.87 ± 24.44; GYKI 52466 FH, 51.10 ± 5.15; FR, 37.25 ± 7.54). Nakong ea ho qala B, ho itšireletsa pele le GYKI 52466 pele bothata ba cocaine bo sitisa ka ho feletseng phapang mosebetsing o hlokometsoeng kamora 'mele oa motlakase pakeng tsa FR le likhomo tsa FH (phekolo ea pele: F(1,16) = 8.52, p = 0.01; phello ea sehlopha: F(1,16) = 8.02, p <0.05; Tšebelisano ea P × G: F(1,16) = 11.07, p <0.001) (Feie. 4). Ha ho liphello tsa koloi khahlanong le naltrexone pele ho ts'oaetso kapa FR ho tloha ho sehlopha sa FH se ne se bonoa liphoofolong nakong ea A (phekolo ea pele ho feta: F(1,16) = 1.03, NS; phello ea sehlopha: F(1,16) = 1.18, NS; ketsahalo ± SEM: FH saline, 28.20 ± 7.24; FR, 58.50 ± 28.31; naltrexone FH, 27.90 ± 8.91; FR, 33.38 ± 8.31). Nakong ea lihlopha tsa B, liphoofolo tsa F tse nkiloeng pele ka naltrexone pele bothata ba cocaine bo hlōleha ho bontša mesebetsi e phahameng ho feta liphoofolo tsa FH tse hlokometsoeng kamora 'mele oa motlakase oa ho itšireletsa. F(1,16) = 4.48, p = 0.05; phello ea sehlopha: F(1,16) = 7.30, p <0.05; Tšebelisano ea P × G: F(1,16) = 7.56, p <0.05) (Feie. 4). Qetellong, SCH23390 ho itšireletsa pele ho fokolisitse ho fokotsa ts'oaetso e hlakileng liphoofolong tsa FR ho bapisoa le liphoofolo tsa FH nakong ea phallo ea A (ho itšireletsa pele: F(1,16) = 13.38, p = 0.05; phello ea sehlopha: F(1,16) = 4.00, NS; P × G ho kopana: F(1,16) = 5.77, p <0.05; ts'ebetso ± SEM: letsoai, FH, 38.20 ± 9.05; FR, 111.87 ± 30.67; GYKI 52466 FH, 25.00 ± 4.13; BOPHELO, 48.12 ± 25.86). Leha ho le joalo, nakong ea B, leha SCH23390 e ile ea fokotsa likarabo tsa cocaine lihlopheng tsena ka bobeli, e ile ea hlōleha ho thibela phapang ea ketsahalo e pakeng tsa FR le likhomo tsa FH (ts'ebetso ea ho itšireletsa pele: F(1,16) = 18.46, p <0.001; phello ea sehlopha: F(1,16) = 7.77, p <0.05; Tšebelisano ea P × G: F(1,16) = 4.05, NS) (Feie. 4).

Leka 6

Tsebo ea lipapali tsa ho kenya lijo li nkiloe ka liphoofolo tsa FR le tsa FH ka ho ba fa monyetla oa ho fumana li-pellets tsa 80 tse tsoileng matsoho nakong ea 5 min. B. Mosebetsi nakong ea matšoao a mabeli a A le B a ne a lebelloa, 'me palo eohle ea liphaephe tse monate li ne li jeoa e lekantsoe. Ketsahalo nakong ea ho matha A e ne e phahame ka liphoofolo tsa F ho feta liphoofolo tsa FH (t(14) = 2.34, p <0.05; ketsahalo ± SEM: FH, 88.14 ± 12.94; BOPHELO, 207.44 ± 49.33). Ka lehlakoreng le leng, tšebetso nakong ea ho matha B (5 min), ha li-pellets tse tsoekere li ne li fumaneha ad libitum, e ne e phahame ka ho fetisisa ho likhomo tsa FH ho feta ka litoeba tsa FR (t(14) = -4.85, p <0.0001; ketsahalo ± SEM: FH, 24.00 ± 3.30; FR, 7.78 ± 1.49). Mosebetsi o tlase liphoofolong tsa FR o ne o bakoa ke ho ja ha tsona lipalo tse tsoekere haholo ho feta liphoofolo tsa FH, joalo ka ha ho hlahisitsoe ka grama (t(14) = 2.70, p <0.05; chelete e sebelisitsoeng ± SEM: FH, 0.78 ± 0.1; FR, 1.08 ± 0.03) kapa e le liperesente tsa boima ba 'mele ea bona (t(14) = 3.58, p <0.01; karo-karolelano ea ho ja ± SEM: FH, 3.05 ± 0.45; FR, 4.77 ± 0.17).

Puisano

Phuputsong ea hona joale, litoeba tse hanngoeng ke lijo, tse atisang ho pepesoa lijo tse monate ka mokhoa o itseng, li bontšitse keketseho e ntseng e tsoela pele le e tsitsitseng mosebetsing oa motlakase ho seo. Ka lehlakoreng le leng, liphoofolo tse fumanang lijo malapeng a bona a lehae, kapa liphoofolo tseo litholoana tsa tsona li neng li khotsofatsoa pele li ne li lekanngoa ke ho satiation, li bontšitse ho fokotseha ha mosebetsi oa ho etsa lintho tse ngata ka mor'a hore li hlahelle ka mokhoa o tšoanang. Dintlha tsena li tšoana le ntshetsopele ya ho hlohlelletsa boitšoaro ho pheta-pheta nako e ngata ho lithethefatsi tsa tlhekefetso tse kang cocaine. Ka mor'a ho hlohlelletsa, ho beha litoeba sebakeng se nang le liaparo, esita leha ho se na lijo, ho ile ha fella ka mosebetsi o moholo. Ka ho hlakileng, bophahamo ba likarabo tse peli (nakong ea matha A), 'me boemo bo tsitsitseng bo holimo haholo ha liphoofolo tsa FR li behiloe moelelong o tšoanang le oo ka oona ba ileng ba fumana lijo tse phetoang khafetsa. Ha ho phapang e khōlō mosebetsing pakeng tsa lihlopha tse ileng tsa hlokomeloa tikolohong e fapaneng le e sa amoheleheng.

Ho tsebo ea rona, liphello tsa rona ke tlaleho ea pele ea ho hlohlelletsa mohaho ho lijo tse natefisang ka litoeba. Thuto e fetileng (Schroeder et al., 2001) ha aa ka a hlokomelloa ke likhoele khafetsa tse pepeselitsoeng ka tsokolate chips liketselong tsa mosebetsi. Leha ho le joalo, ho fapana le thuto ea hona joale, liphoofolo e ne e se lijo tse lahliloeng. Ka hona, matla a fokolang a matla a matla a ka 'na a e-ba a bohlokoa ho theha mokhoa oa ho hlohlelletsa batho ba nang le lijo. Thibelo ea lijo ka bobeli e thusa phetisetso ea dopaminergic, haholo-holo nucleus accumbens (Cadoni et al., 2003; Carr et al., 2003; Haberny et al., 2004; Lindblom et al., 2006), 'me e eketsa matlotlo a khotsofatsang le a susumetsang a dopamine receptor agonists (Carr et al., 2001) le lithethefatsi tse susumetsang (Deroche et al., 1993; Bell et al., 1997; Cabeza de Vaca et al., 2004). Ho tsamaisoa ha phetisetso ea dopaminergic nucleus accumbens, le polasetiki ka litsela tse amanang (Haberny et al., 2004; Haberny le Carr, 2005) e ka 'na ea e-ba ntho ea bohlokoa bakeng sa ho theha mokhoa oa ho khothaletsa boitšoaro.

Ho bapisa tlhahiso ea lijo le ho hlohlelletsa boitšoaro ho lithethefatsi tsa tlhekefetso ho senola likarolo tse 'maloa tse tloaelehileng. Ho khothaletsa boitšoaro ho lithethefatsi tse lemalang ho tsoela pele ka likhoeli ka mor'a hore phekolo e khaotse (Paulson et al., 1991; Moqapi le Goldman-Rakic, 1999). Phuputsong ea hona joale, karabelo ea bobeli le tekanyetso ea phekolo ea lijo e ile ea tsoela pele ka nako ea libeke tse 3 ntle le ho pepesehela tikoloho ea liaparo, e bontšang hore likarabo tsena ka bobeli li bile teng ka nako e telele. Ha re e-s'o hlahlobe nako e telele.

Ha re fumana hore lijo tse tsamaisanang le lijo li na le bokhoni ba ho hlahisa karabo ea mokolosi oa maemo a lumellanang le ho shebella (Bindra, 1968) hore tšusumetso e mabapi le tikoloho e kopantsoeng le basebetsi ba ka sehloohong ba matlafatsang e etsa hore ho be le mosebetsi o motle, phello e 'nileng ea tiisoa khafetsa (Jones le Robbins, 1992; Hayward le Low, 2005; Barbano le Cador, 2006). Ho feta moo, mosebetsi oa ho lokisa o hlokometsoe ka lijo-liphoofolo tse hlokomelisoang tse pepeneneng le maemo a lijo ha li ne li sa amoheloe, li ne li tšoana le ka boholo ba mosebetsi oa tsona o lekantsoeng ha lijo li fumaneha. Sephetho sena se fana ka maikutlo a hore mosebetsi o hlokomelisitsoeng oa batho ba sebetsang ha o arabela ka lijo li fana ka karabelo ho tikoloho, ho e-na le ho fanoa ke lijo.

Ho thehoa ha ts'ebeliso ea boitšoaro le boits'oaro bo sebetsanang le lithethefatsi bo itšetlehile ka mekhoa e amanang le mefuta e meng ea nako e telele ea tšebetso, ka hore liketsahalo tsena li koetsoe ke bahanyetsi ba NMDA, protheine synthesis inhibitors le dopamine D1 bahanyetsi. Mekhoa e tšoanang ha e hlokehe ka ho khetheha bakeng sa polelo ea ts'ebetso kapa ts'ebeliso ea boemo, e bonahalang eka ha e itšetlehe haholo ka D1 mekhoa e amohelehang ea mofuthu (Beninger le Hahn, 1983; Cervo le Samanin, 1996; McFarland le Ettenberg, 1999). Leha ho le joalo, tlhahiso ea cues predictive bakeng sa ho fumaneha ha sucrose e hlahisa ho lokolloa ha dopamine nucleus accumbens (Roitman et al., 2004), ho fana ka maikutlo a hore karolo e ka 'nang ea e-ba teng bakeng sa li-receptor tsa dopamine ka karabo e entsoeng ke lijo. Thutong ea hona joale, ha ho D1 mohanyetsi SCH23390 kapa D2/D3 mohanyetsi oa sulpiride o hanyetsa ka mokhoa o tsitsitseng polelo ea ho lokoloha ha boemo, maemong a seng a ntse a atisa ho fokotsa mesebetsi ea basal. Ka hona, ts'ebetso ea D1 le D2/D3 li-receptors li ka bapala karolo e sa reng letho pontsong ea liketso tsa boemo ba lijo, joalo ka ka liketso tsa lithethefatsi.

Ho iketelletsa pele le mohanyetsi oa opiate naltrexone o ile oa felisa mosebetsi o pholileng oa lijo liphoofolong tsa FR, empa o ne o se na phello e fokolang mosebetsing oa taolo, ho fana ka maikutlo a hore li-receptors tsa opioid li kenngoa mofuteng oa kutloisiso e bakoang ke lijo. Ha re tsebe data mabapi le liphello tsa thibelo ea opioid ka polelo ea ho khothaletsoa ha cocaine, le hoja naltrexone e thibela polelo ea boitšoaro ba sensitization ho methamphetamine (Chiu et al., 2005). Bokhoni ba mohanyetsi e mong oa opioid, naloxone, ho fokotsa ho arabela ha basebetsi bakeng sa li-reinforcers (Glass et al., 1999) le mosebetsi oa boipheliso ba ho ja lijo ka pel'a lijo (Hayward le Low, 2005), hammoho le bokhoni ba μ-agonist morphine ho kenyelletsa moelelo-taba o itšetlehileng ka ho fepa (Kelley et al., 2000) e fana ka maikutlo a bohlokoa bakeng sa li-receptor tsa opiate li arabelletsang lijo.

Khatelo-pele le polelo ea ts'oaetso ea lik'hemik'hale tse bakoang ke k'hok'heine e amahanngoa le liphetoho tse bakoang ke ho ntšetsa pele ha methapo ea matšoao (glutamatergic neurotransmission)Wolf, 1998; Vanderschuren le Kalivas, 2000). Har'a li-receptor tse nang le glutamate, li-receptors tsa AMPA li bonahala li ameha ka ho khetheha ho laola polelo ea liketso tse entsoeng ka lik'hemik'hale tse nang le lithethefatsi (Pierce et al., 1996; Li-Cornish le Kalivas, 2001; Carlezon le Nestler, 2002; Boudreau le Wolf, 2005), le bahanyetsi ba NPQX ba nang le tlhōlisano ea AMPA [2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) -quinoxaline] le DNQX (6,7-dinitroquinoxaline-2,3-dione) e thibela mosebetsi o entsoeng ka boemo bo itseng ho amphetamine le k'hok'heine ka litoeba (Cervo le Samanin, 1996; Mead le Stephens, 1998; Mead et al., 1999). Lintlheng, GYKI 52466 ea mohanyetsi oa AMPA ea sa amoheleheng e thibela likarabo tsa lik'hemik'hale (cocaine)Hotsenpiller et al., 2001). Phuputsong ea hona joale, GYKI 52466 e felisitse ketso ea boemo ba lijo, ntle le tšusumetso ea ho etsa lintho tse itekanetseng (nakong ea pele ea metsotsoana ea 5 ea ho matha), e fana ka maikutlo a hore polelo ea liketso tsa lijo, joaloka ts'ebetso ea lithethefatsi, e itšetlehile ka ts'ebetso ea AMPA li-receptors.

Hang ha liphoofolo li khothalletsoa ke lithethefatsi tse le 'ngoe, li atisa ho bonts'a meriana e meng (Vezina et al., 1989). Thutong ea hajoale, bokhoni ba cocaine le morphine ba ho eketsa ts'ebetso ea li-locomotor bo ntlafalitsoe haholo liphoofolong tse matlafalitsoeng ke lijo, ha li bapisoa le sehlopha sa taolo. Le ha karabelo ena e eketsehileng e ka hlalosoa e le ho hlohlelletsa batho ba bang sefapanong, ak'haonte e 'ngoe ke hore matla a k'hok'heine kapa morphine a ho susumetsa tšebetso a bonoa habonolo ha liphoofolo li ne li se li ntse li bonts'a matla a ntlafetseng tikolohong e nang le lijo (Stephens le Mead, 2004). Leha ho le joalo, hobane ka tekong ea lipuisano, ho pepeseha ha amphetamine nakong e fetileng ho etsa hore motho a amohele likarabo tsa lijo (Jones et al., 1990; Avena le Hoebel, 2003), ho ka 'na ha e-ba le hore ho lumellana le moelelo oa lithethefatsi kapa liphello tsa lijo ho etsa hore ho be le mokhoa oa ho fana ka lipontšo ka litsela tse tloaelehileng.

Ho hlohlelletsa boitšoaro ho ka talingoa e le phello ea mekhoa ea ho ithuta ea ho kopanya likokoana-hloko e amanang le boemo ba lithethefatsi-tikoloho. Ho ea ka pono ena, tsamaiso ea meriana e ts'oanang ea meriana e lumellanang le maemo a lumellanang le maemo a lumellanang le maemo a lumellanang le maemo a lumellang hore ho be le litšobotsi tse hlahisoang ke moea (CS). Tlhaloso ea CS feela (moelelo oa taba) e ba e lekaneng ho hlahisa karabo e kang ea lik'hemik'hale. Hobane mokhatlo oa lihlahisoa tsa tikoloho le moputso o lokela ho ithutoa, mokhoa oa ho ithuta, ho e-na le phello ea lithethefatsi, o fana ka ts'ebeliso e matla ea boitšoaro bo botle ba boitšoaro (Tilson le Rech, 1973; Pert et al., 1990). E sebelisitsoe ho hlollang ha ho tšoaetsanoa ha sefapano, tlaleho ena e bolela esale pele hore lithethefatsi tse thibelang ho boleloa ha mosebetsi o hlophisitsoeng li lokela hape ho thibela ho khothaletsoa ho feta ho feta meputso e meng. Re lekile ts'ebetsong ena liphoofolong tse nang le lijo, ka ho fana ka GYKI 52466 le naltrexone pele re ba pepesa k'hok'heine. Boipelaetso bobeli bo ne bo sitisa tšusumetso ea mokokotlo ho liphello tse susumetsang tsa cocaine. Ka lehlakoreng le leng, ho itšireletsa pele SCH23390, e ileng ea hlōleha ho thibela mosebetsi o tsitsitseng ka liphoofolo tsa F, ho fokotseha mosebetsi oa lihlahisoa lihlopheng tsena ka bobeli, empa o ile oa hlōleha ho thibela ho khothaletsoa ho tšoaetsanoang ha cocaine. Ka hona, ho khothaletsoa ha mokokotlo ho li-cocaine tse bolokiloeng liphoofolong tse fepehileng ka lijo ho bonahatsa liphello tse bohloko tsa moriana ka mokhoa oa ho arabela ka mokhoa o lumellanang le tikoloho e tsamaeang ka lijo.

Ka kakaretso, liphello tsa hona joale li bontša hore tlhahiso ea boitšoaro ha e hlahe feela ka lithethefatsi tsa tlhekefetso, empa hape le moputso oa tlhaho, lijo le hore mefuta ena ea ts'ehetso e na le litšobotsi tse ngata tse tšoanang. Ka lehlakoreng le leng, boitsebiso ba hona joale bo bontša hore bokhoni ba litlhohonolofatso tsa tlhaho ho tšehetsa boits'oaro ba boits'oaro le boits'oaro bo kenyelletsoeng bo ka 'na ba bolela karolo ea ho matlafatsoa ho susumelletsa batho hore ba fumane lijo. Ka lehlakoreng le leng, ba ka 'na ba fana ka maikutlo a hore karabo ea potso ea hore na ke hobane'ng ha ho batla lithethefatsi ho lebisa boitšoaro, ka tsela eo ka eona mokhoa o tloaelehileng oa ho batla moputso (Robinson le Berridge, 1993, 2001), ha e itšetlehe ka bokhoni ba lithethefatsi ho tšehetsa ho khothatsa boitšoaro.

Qetellong, re ile ra botsa hore na boemo ba tikoloho ho lijo bo bakoang ke tikoloho-bo amanang le ho eketseha mosebetsing, bo ka boela ba ama boitšoaro ba ho fepa. Tlhaloso e hlakileng kapa e khanyang, e kopantsoeng le lijo ha litoe ke lijo tse lahliloeng, ka mor'a moo li etsa hore li fepe (Petrovich et al., 2002; Holland le Petrovich, 2005); ka tsela e tšoanang, litoeba tse nang le phepelo tse jeoang ke lijo tse jang lijo tse ngata ho feta sehlopha sa taolo se nang le tšebetso e tšoanang le ea litsela, empa e kile ea e-ba le lijo tsa morao-rao matlong a lehae. Ka lebaka leo, tikoloho e nang le maemo a eketsehileng e eketsa lijo tse sebelisoang, mohlomong ka bokhoni ba li-CS tse joalo ho kenya menyetla ea amygdala ho hypothalamus lateral ka accumbens le prefrontal cortex (Petrovich et al., 2005). Ho sa tsotellehe hore na ho na le bokhoni ba ho eketsa mosebetsi oa ho lokisa le ho susumelletsa ho fepa ho itšetlehile ka literekeng tse amanang le tsona, le hore na tsena li tšoana le lipotoloho tse sebelisoang nakong ea ho khothaletsa boitšoaro ho lithethefatsi ke potso e thahasellisang.

Mongolo o botlaaseng ba leqephe

  • Re amohetse December 15, 2005.
  • Phetolelo e amohetse May 26, 2006.
  • E amohetse May 27, 2006.

  • Re leboha Robin Phillips, Chiara Giuliano, le Rosie Pyper ho thusa ho etsa liteko le Pete Clifton bakeng sa litlhaloso tse thusang ho ngoloa ha buka ena e ngotsoeng ka letsoho.

  • Puisano e lokela ho lebisetsoa ho David N. Stephens, Lefapha la Psychology, Sekolo sa Bophelo sa Sciences, Univesithi ea Sussex, Falmer, Brighton BN1 9QG, UK. Imeile: [imeile e sirelelitsoe]

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