Tšebelisano ea Sechaba e Fokotsa Matlotlo a Putsang a Amphetamine ka Dopamine D1 Receptor-Mediated Mechanism (2011)

J Neurosci. Sengoloa se ngotsoeng; e fumaneha ho PMC Dec 1, 2011.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC3114880

NIHMSID: NIHMS300918

Phetolelo ea ho qetela ea sengoliloeng sa sengoliloeng sena e fumaneha mahala ho J Neurosci

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

Eya ho:

inahaneloang

Leha litlamorao tsa ts'ireletso ea litlamo tsa kahisano mabapi le tšebeliso ea lithethefatsi / tlhekefetso li ngotsoe hantle, ha re tsebe letho ka mekhoa e ka tlase e sebelisang methapo ea kutlo. U sebelisa tlotlo ea prairie (Microtus ochrogaster) - - molumo o kopaneng sechabeng o etsang litlamo tsa nako e telele kamora ho nyalana — re bonts'a boemo ba amphetamine (AMPH) bo kenyelletsang khetho ea sebaka se ikhethileng (CPP) ka thobalano naïve (SN), empa e se balekane-ba babeli (PB), banna. Le ha kalafo ea AMPH e bakile boholo bo ts'oanang ba ho lokolloa ha DA ka har'a li-nucleus accumbens (NAcc) tsa banna ba SN le PB, e bile le litlamorao ho NAcc D1 receptor (D1R) binding. Ka ho khetheha, kalafo ea AMPH e ile ea eketsa tlamo ea D1R ho SN, empa ea fokotsa D1R e tlamang ho banna ba PB. NAcc D1R, empa eseng D2R, antagonism e thibetse CPP e kenyellelitsoeng ho banna ba SN le NAcc D1R ts'ebetso pele boemo ba AMPH bo nolofalletsa AMP-induction CPP ho banna ba PB. Hammoho, datha ea rona e bonts'a hore boiphihlelo bo kopanyang bo fokotsa thepa e ruisang ea AMPH ka mochine o kopanetsoeng oa D1R.

SELELEKELA

Hoa tsebahala hore tšebeliso ea lithethefatsi le tlhekefetso e na le litlamorao tse matla mekhoeng e fapaneng ea boits'oaro, ho kenyelletsa bonto ba sechaba (Bacha et al., 2011a). Ntle le moo, lintlha tsa kahisano, joalo ka ho ba teng kapa ho ba sieo ha likamano tse matla tsa sechaba nakong ea ntšetso-pele kapa nakong ea ho ba motho e moholo, li ka ama tšebeliso ea lithethefatsi le ho ba kotsing ea tlhekefetso ea lithethefatsi. Mohlala, kamano e matla ea motsoali ea lilemong tsa bocha e ts'oantsoe le mathata a fokotsehileng a mathata a ts'ebeliso ea lithethefatsi (Ellickson et al., 1999; Bell et al., 2000). Ho feta moo, bathong ba seng ba lemaletse, likamano tse haufi pakeng tsa balekane ba thusana ho hlaphoheloa bokhobeng ba lithethefatsi (Kosten et al., 1987). Ka lehlakoreng le leng, kamano e fokolang ea sechaba e ka eketsa tlhekefetso ea tlhekefetso ea lithethefatsi joalo ka ha mekhoa ea batho ba baholo ba sa sireletsehang e amana hantle le tlhekefetso ea joala le tlhekefetso e seng molaong (Brennan le Shaver, 1995; Vungkhanching et al., 2004; Caspers et al., 2005).

Mekhoa ea neural e sebelisang tšebelisano lipakeng tsa tlamahano ea bophelo bo haufi le tšebeliso ea lithethefatsi / tlhekefetso e ntse e sa tsejoe haholo, leha ho le joalo, tsamaiso ea mesolimbic dopamine (DA)-haholo-holo li-neurotransuction tsa DA kahare ho li-nucleus accumbens (NAcc) - li ka nka karolo (Bacha et al., 2011a). Lithuto sebakeng sa prairie vole (Microtus ochrogaster- - selekane se kopaneng sechabeng se kopanyang maqhama a pakeng tsa balekane ba baholo (ke hore, litlamo tsa balekane) (Insel le Hulihan, 1995; Mattson et al., 2001) - re bonts'itse hore NAcc DA e kena lipakeng le ho e lokisaGingrich et al., 2000; Aragona et al., 2003; Aragona et al., 2006). Ho feta moo, neurotransication ea Nacc DA e buelloa ke lithethefatsi tsohle tse tsebahalang tsa tlhekefetso (Di Chiara le Imperato, 1988; Bergman et al., 1990; Koob le Nestler, 1997; Nestler, 2005) le likhopotso tse tsoang khafetsa tsa psychostimulant tse hlahisang lithethefatsi tse lokolloang ke DA le ho utloa ha li-receptor hammoho le morphology ea NAcc neurons (Henry et al., 1989; Robinson le Kolb, 1999). Liphetoho tsena ho nahanoa hore li etsa liphetoho tse tlisoang ke lithethefatsi maemong a boitšoaro (Robinson le Becker, 1986), ho kenyelletsa boitšoaro ba sechaba (Fiorino le Phillips, 1999).

Joalo ka ha bobeli bo kopanetsoeng boits'oaro le taolo ea ona ke li-neurotransmission tsa DA kahare ho NAcc li bonahalitsoe hantle sebakeng sa praeree vole (Gingrich et al., 2000; Aragona et al., 2003; Aragona et al., 2006), ho entsoe boiteko ba morao-rao ba ho hlahisa mofuta ona e le mohlala oa phoofolo moo ho hlahlojoang tšebelisano ea boitšoaro lipakeng tsa tlamahano ea bophelo bo haufi le tšebeliso ea lithethefatsi / tlhekefetso, hammoho le mekhoa ea eona e ka tlase ea tlhaho. AMPH e bontšitsoe hore e na le thepa e ruisang molemo libakeng tsa prairie, joalo ka ha boemo ba AMPH bo etsa hore motho a rate maemo (CPP) ka bobeli ba bong (Aragona et al., 2007; Liu et al., 2010; Bacha et al., 2011b), mme ts'ebetso ena e kopantsoe ke neurotransmission ea DA ho NAcc (Curtis le Wang, 2007; Liu et al., 2010). Ho khahlisang le ho feta, ho pepesetsoa hoa AMPH ho thibela ts'ebetso ea litabatabelo tsa balekane ba kopantsoeng le litheko tse ts'oaroang ke balekane mme mokhoa ona oa ts'ebetso oa AMPH o kopantseng — bonyane ka karolo - ke NAcc DA D1-mofuta receptor (D1R) activationLiu et al., 2010). Phuputsong e teng hona joale, re fuputse litlamorao tsa maqhama a kopantsoeng a le babeli ho CPP e kenyellelitsoeng ho batho ba babeli. Re ile ra kholoa hore boiphihlelo ba maqhama a kopaneng bo tla fokotsa litlamorao tsa AMPH le hore NAcc DA e ka ameha ketsahalong ena ea boitšoaro.

LISEBELISOA LE MEKHOA

Lihlooho

Makala e ne e le li-voes tsa praemia tsa banna (M. ochrogaster) Ho tsoa koloneng ea maiketsetso. Lintho li ile tsa khoesoa ka nako ea matsatsi a 21 'me tsa bolokoa ka ba babeli ho ngoan a ngoanana a le mong ka mekotla ea polasetiki (12 x 28 × 16 cm). Ho ile ha fanoa ka metsi le lijo ad libitum. Litsela tsohle li ne li bolokoa tlasa 14: 10 potoloho e lefifi mme mocheso o ne o bolokiloe ho 20 ° C. Lintho tse haufi le matsatsi a 75 tsa lilemo li ne li lula li lula ka bolona le ngoan'abo ngoanana a le mong (mme ka hona ba ile ba boloka thobalano naïve (SN)) kapa ba penta le mosali ea sa kopaneleng libeke tse peli ho ba tlamahano ea lenyalo. Ka bobeli lithuto tsa SN le PB li ile tsa lekoa ka nako e ka bang matsatsi a 90.

Boemo ba AMPH le tlhahlobo ea CPP

Ts'ebetso tsena li entsoe joalo ka ha ho hlalositsoe pele (Liu et al., 2010; Bacha et al., 2011b). Ka bokhutšoanyane, lisebelisoa tsa liteko tsa CPP li ne li kenyelletsa mekotla e 'meli (12 × 28 × 16 cm); e le 'ngoe e ntšo e nang le tšepe ea tšepe holimo le e' ngoe e tšoeu ka sehokelo sa mathe, e kopantsoeng ke tube e se nang letho (7.5 × 16 cm). Le ha li-voes tsa prairie ka kakaretso li rata ho khetha tse tšoeu ho kokoana-hloko e lefifi (Aragona et al., 2007), ho na le phapang e kholo ea motho ka mong khetho ena. Ka hona, ka letsatsi la 1, re ile ra leka lithuto tsohle bakeng sa likhetho tsa bona tsa pele tsa cage nakong ea tlhahlobo ea pele ea 30 min. Nakong ea tlhahlobo ena, lithuto tsohle li ne li lumelloa ho fihlella mahala ho tseko ka bobeli re bile re lekanyetsa nako eo motho ka mong a e sebelisang khorong ka 'ngoe. Ka matsatsi 2-4, lithuto li ile tsa fumana likarolo tse peli tsa boemo ba 40, 6 hrs ntle le e mong. Sebokeng sa hoseng, lithuto li fumane 1.0 mg / kg AMPH (Sigma, St. Louis, MO, USA) e qhibilihile ka lihlopha tsa 0.9% saline (SN-AMPH le PB-AMPH) kapa sa saline feela (Li-SN-saline le PB-saline lihlopha ) 'me tsa kenngoa ka har'a teraka eo ba ileng ba qeta nako e nyane nakong ea tlhahlobo ea pele (e nang le likhopo). Lenaneong la thapama, lithuto tsohle li ile tsa fumana ente ea letsoai 'me tsa kenngoa ka lekaleng le leng. Letsatsing la 5, lithuto li ile tsa boela tsa lekoa bakeng sa likhetho tsa cage ho liteko tsa morao-rao tsa 30. Hang ka mor'a tlhahlobo ea kamora 'lithupelo, lithuto li ile tsa hlakoloa ka potlako' me meea ea tsona ea hoama leqhoeng le omisitsoeng. Likarolo tsa boko li ile tsa sebetsoa kamora nako bakeng sa D1R le DA D2-mofuta receptor (D2R) autoradiographic binding.

Bacteria micodialysis le HPLC-ECD tlhahlobo

Lipatlisiso tsa Microdialysis li entsoe joalo ka ha ho hlalositsoe pele (Curtis le Wang, 2007) mme ba kenngoa kahare ho NAcc (li-link tsa stereotaxic tse tsoang ho bregma: anterior 2.1 mm, lateral 0.6 mm, ventral 6.3 mm) tlasa sodium pentabarbitol anesthesia (1mg / 10kg boima ba 'mele). Liphoofolo li ile tsa lumelloa ho hlaphoheloa bosiu 'me tsa lekoa hoseng se latelang. Liphetho li entsoe ka mokhoa o tsoelang pele ho 2.3 µl / min ka tharollo ea isotonic ea sodium, potasiamo, calcium le magnesium (144 mM NaCl, 2.8 mM KCl, 1.2 mM CaCl2 le 0.9 mM MgCl2 (E sirelelitsoe le Curtis, 1993)).

Kamora ho hlaphoheloa bosiu bo le bong, mehlala e mene ea 20 ea nakoana e ile ea bokelloa likotong tse nang le 5µl ea 0.1N perchloric acid. Kamora moo, lithuto li ile tsa fumana ente ea intraperitoneal (ip) ea AMPH (1.0mg / kg) le disampole tsa dialysate li ile tsa bokelloa ka mokhoa o tsoelang pele libakeng tsa 20 tsa metsotso bakeng sa 3 hrs. Mefuta ea Dialysate e ile ea hoamisoa hang-hang ho −80 ° C ho fihlela ho hlahlojoa. Palo ea DA le DOPAC mohlaleng ka mong e ne e behiloe molemong oa ho sebelisa sesebelisoa se phahameng sa chromatography ka tlhahlobo ea motlakase (HPLC-ECD) joalo ka ha ho hlalositsoe pele (Curtis le Wang, 2007). Qetellong ea nako ea ho etsa sampole, ho ile ha etsoa mahlabelo ho etsoa tlhahlobo ea tlhahlobo ea tlhahlobo-leseling.

DA receptor autoradiography

Likarolo tsa boko ba Coronal (20 µm) mahareng a 120-µm li ile tsa sebetsoa molemong oa ho kopanya DA receptor autoradiographic ho sebelisa mokhoa o thehiloeng (Aragona et al., 2006). Ka bokhutšoanyane, likarolo li ile tsa qhekelloa ka 50 mM Tris-HCl (pH 7.4) mme e kentsoe ka 50 mM Tris-HCl ion buffer e nang le 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 le 1 mM MgCl2 ka le [125I] SCH23982 (D1R ligand) kapa [125I] 2'-iodospiperone (D2R ligand) (PerkinElmer). Kamora moo, likarolo li ile tsa hlophisoa ho 0.1% paraformaldehyde 'me ea hloa ka botlalo ho Tris-HCl ion buffer. Li-Slide li ile tsa kenngoa ka metsing a halikiloeng, tsa otloa ka ho omella 'me tsa pepesetsoa filimi ea BioMax MR (Kodak) ho hlahisa li-autoradiograms. Methapo ea sefahleho ea D1R le D2R e neng e kopantsoe le NAcc le CP li ile tsa hlakoloa ka likarolo tsa boko tsa 3 tse nang le sebopeho ka seng ho phoofolo e tsoang ho li-autoradiograms li sebelisa lenaneo la setšoantšo sa k'homphieutha (NIH IMAGE 1.64).

Stereotaxic cannulation le microinjection

Lintho li ile tsa sebelisoa ntle le tšebeliso ea sodium pentobarbital le 26-gauge biliveal steel cannulae (Plastics One Inc., Roanoke, VA) li kentsoe stereotaxically mme li reretsoe ho NAcc, joalo ka ha ho hlalositsoe pele (Aragona et al., 2003). Lintho li ile tsa lumelloa ho hlaphoheloa matsatsing a 3-7. Ka le leng la matsatsi a 3 a boemo ba boemo, 30 min pele ho ente ea AMPH, lithuto li ile tsa fumana li-microinjection tsa mohlomong mokelikeli oa methapo ea methapo (CSF; 200nl / lehlakoreng) kapa CSF e nang le agonist ea D1R, SKF 38393, mohanyetsi oa D1R, kapa SCH 23390, kapa SCH 2, kapa SCH XNUMX, kapa SCH XNUMX, kapa SCH XNUMX, kapa SCH XNUMX, kapa SCH XNUMX Mohanyetsi oa DXNUMXR, eticlopride (Sigma, St. Louis, OH). Kamora tlhahlobo ea CPP, lithuto tsohle li ile tsa hlakoloa ka potlako 'me methapo ea tsona ea huloa ho netefatsa libaka tsa ente ea nalane ka nalane. Lintho tse nang le likanono tse sa sebetsoang hantle li ile tsa behelloa ka thoko ho tlhaiso-leseling.

Tlhatlhobo ea data le tlhahlobo ea lipalo

CPP e ile ea khethoa ke mehlala ea lipara t teko ho bapisa nako eo lithuto li e qetileng kolecheng e boemo bo lipakeng tsa liteko tsa pele le tsa kamora 'lithupelo. Likheo tsa Cage lipakeng tsa liteko tsa pele le tsa kamora 'lithupelo li ile tsa hlahlojoa hape ke a t teko ea ho lekola hore na AMPH kapa agonist ea D1R kapa D1R kapa D2R kapa antagonist e amme ts'ebetso ea locomotor. Palo ea mantlha ea motheo ea DA le DOPAC ka li-dialysates li ne li bapisoa pakeng tsa lihlopha tse sebelisang a t tlhatlhobo. Bakeng sa tekolo ea litlamorao tsa AMPH ka nako eohle, lipalo tsa DA le DOPAC mohlaleng o mong le o mong oa sampole le post-AMPH li hlahisitsoe e le liperesente tsa palo ea motheo ea basement. Litekanyetso tsena li ile tsa hlahlojoa ke mehato e phetoang ANOVA e lateloang ke tlhahlobo ea posthoc ea Student-Neuman-Keuls (SNK). Kamora nako, liphapang tsa sehlopha litekong tsa D1R le D2R tse tlamang ho NAcc le CP li ile tsa hlahlojoa ke ANOVA ea mekhoa e 'meli e lateloang ke liteko tsa SNK posthoc.

Moralo oa liteko

Teko 1 e ne e etselitsoe ho senola litlamorao tsa boiphihlelo ba maqhama ho CPP e kenyellelitsoeng ho CPP. Ba batona ba SN le PB ba ile ba hlahlojoa pele ho lisebelisoa tsa CPP. Ka mor'a moo ba ne ba arotsoe ka lihlopha tsa 4 tse ileng tsa amohela liente tsa saline (n = 5 ea SN le n = 9 bakeng sa banna ba PB) kapa AMPH (1.0mg / kg; n = 8 bakeng sa banna ba SN le n = 8 bakeng sa ba batona ba hoseng ba hoseng. ka matsatsi a mararo a latelang (Liu et al., 2010). Kamora moo, lithuto tsohle li ile tsa fumana tlhahlobo ea tlhahlobo ea posta ea CPP.

Teko ea 2 e bapisitse ho lokolloa ha AMPH-induction DA ho NAcc pakeng tsa SN (n = 6) le banna ba PB (n = 5). Lintho li ile tsa kenngoa ka lipatlisiso tsa microsalysis tse lebisitsoeng ho NAcc. Kamora ho hlaphoheloa bosiu bo le bong ka motsoako o sa khaotseng oa tharollo ea isotonic ka li-probes, mehlala e mene ea 20 min baseline dialysate e ile ea bokelloa. Kamora moo, lithuto li ile tsa fumana ente ea ip ea AMPH (1.0mg / kg) mme disampole tsa dialysate li ile tsa bokelloa ka mokhoa o tsoelang pele metsotso e meng le e meng ea 20 bakeng sa lihora tsa 3. Lipampiri tsena li ile tsa hlahlojoa kamora nako bakeng sa likakanyo tsa DA le 3,4-Dihydroxyphenylacetic acid (DOPAC) li sebelisa tlhahlobo ea HPLC-ECD (Curtis le Wang, 2007).

Teko 3 e ile ea lekola phello ea litšebelisano lipakeng tsa tlamahano ea kalafo le kalafo ea AMPH ho li-receptor tsa DA ho NAcc. Likarolo tsa boko ho tsoa lithutong tse lekiloeng ho Teko ea 1 li ile tsa sebetsoa bakeng sa D1R le D2R e tlama e sebelisa li-receptor autoradiography.

Teko 4 e ile ea leka karolo ea li-receptor tsa NAcc DA ho CPP e kenyellelitsoeng. Banna ba SN ba ne ba kentsoe li-cannulae ka tsela e habeli e etselitsoeng NAcc. Kamora ho hlaphoheloa ha 3 d, lithuto li ile tsa fumana tlhahlobo ea tlhahlobo ea CPP 'me ka mor'a moo tsa abeloa ho se seng sa lihlopha tsa liteko tsa 5 tse amohetseng li-ente tsa NAcc tsa CSF (n = 8) kapa CSF e nang le tlase (4ng / side; n = 8 ) kapa phahameng (100ng / side; n = 6) lethal dose ea mohanyetsi oa D1R, SCH 23390, kapa e tlase (4ng / lehlakoreng; n = 8) kapa phahameng (100ng / side; n = 7) lethal dose ea mohanyetsi oa D2R, eticlopride. Lilemo tse mashome a mararo hamorao, lithuto li ile tsa fumana ente ea AMPH (1.0mg / kg; ip). Ts'ebetso ena e ile ea phetoa matsatsi a 3 a latellanang nakong ea boemo ba AMPH. Kamora moo, lithuto li ile tsa fumana tlhahlobo ea kamora 'CPP.

Teko ea 5 e ile ea hlahloba karolo ea NAcc D1Rs ho sebelisana le li-CPP tse kenyellelitsoeng ho banna ba PB. Lithuto tsa PB li ile tsa aroloa ka lihlopha tse tharo tse ileng tsa amohela liente tsa intra-NAcc tsa CSF (n = 10) kapa CSF e nang le agonist ea D1R, SKF 38393 (0.4ng / lehlakoreng; n = 12), kapa mohanyetsi oa D1R, SCH 23390 (4ng / lehlakoreng , n = 10), pele ho boemo ba AMPH. Cannulation ea Brain, liente tsa AMPH, le liteko tsa CPP li ne li tšoana hantle joalo ka ha ho hlalositsoe ho Teko ea 4.

LIPOTSO

Phihlelo ea bonding ea Pair e fokotsa thepa e ruisang ea AMPH

Phuputsong ea rona e fetileng, kalafo ea AMPH e sitisitse likamano tsa balekane ba hlonephang litšusumetso tsa ba batona, e bonts'ang phello e thibelang ho pepeseha hoa AMPH ka boitšoaro bo kopaneng (2).Liu et al., 2010). Thutong e teng hona joale, re lekile kamano ea boiphetetso: litlamorao tsa ho tlamahana ka bobeli ka moputso oa AMPH. Matsatsi a mararo a boemo ba 1.0 mg / kg AMPH a hlohlelletsa CPP ho banna ba SN (t = 2.45, p <0.05) empa eseng ho banna ba neng ba kopantsoe le e motšehali bakeng sa libeke tse 2 (ke hore, banna ba PB) (Setšoantšo sa 1a). Liente tsa saline ha lia ka tsa ama sehlopha sena ka bobeli. Taba ea bohlokoa ke hore ha ho na phapang e fumanoeng khafetsa ea likhomo tsa liphoofolo tse tšelang lipakeng tsa liteko tsa pele le tsa kamora ho fana ka maikutlo a hore CPP e sotlehileng ho banna ba PB e ne e se ka lebaka la ts'ebetso e fetotsoeng nakong ea tlhahlobo ea boits'oaro.Setšoantšo sa 1b).

Setšoantšo sa 1  

Amphetamine (AMPH) e nang le maemo e etsa hore motho a rate maemo (CPP) ka thobalano naïve (SN) empa e se baratuoa ba tlotsitsoeng (PB) ba batona ba batona ba banna. (a) Banna ba SN kapa PB ba amohetseng saline (SN-saline kapa PB-saline, ka ho latellana) nakong ea matsatsi a 3 ...

Phekolo ea AMPH e etsa hore ho lokolloe ha DA ho NAcc ho banna ba SN le PB

Ha ho na phapang e kholo lipakeng tsa ba batona ba SN le PB ka bongata ba DA kapa DOPAC ho mehlala ea basele ea micodialysis.Setšoantšo sa 2, li-insets). Tsamaiso ea AMPH e hlahisitse keketseho e kholo ho extracellular DA (F(12, 108) = 8.42, p <0.001). Leha ho le joalo, boholo le bolelele ba keketseho ena li ne li sa fapane lipakeng tsa banna ba SN le PB-Maemo a DA a ne a phahame haholo ho feta metheo ea mantlha lihlopheng ka bobeli bakeng sa nako ka 'ngoe ho tse peli tsa pele tsa mehlala (40 min kakaretso) ebe butle e khutlela molemong oa mantlha (Setšoantšo sa 2, konopo e kaholimo). Tsamaiso ea AMPH e fokotsehile haholo extracellular DOPAC ho NAcc ho banna ba SN le PB (F(12, 108) = 13.54, p <0.001), hape, litlamorao tsena li ne li tšoana lihlopheng ka bobeli. Ha ho banna ba SN kapa ba PB ba ileng ba boela ba fumana maemo a mantlha pele sampole e fela (Setšoantšo sa 2, phanele e tlase).

Setšoantšo sa 2  

Maemo a extracellular dopamine (DA) le 3,4-Dihydroxyphenylacetic acid (DOPAC) ka har'a nucleus accumbens (NAcc) ea balekane ba botona le botšehali (SN) le ba batlana (PB) ba latelang kalafo ea amphetamine. Litefiso tse felletseng tsa DA le DOPAC ho li-dialysates tsa motheo ...

Kalafo ea AMPH e fapana ka tsela e fapaneng e fetolang D1R e tlamang ho NAcc ea SN le banna ba PB

Liphuputso tse fetileng li bontšitse hore kalafo ea AMPH e ntlafatsa mofuta oa NAcc D1R le polelo ea protheine (Liu et al., 2010). Ntle le moo, boiphihlelo ba maqhama a kopanyang li phahamisa D1R e tlamang (Aragona et al., 2006) ho NAcc ea li-voes tsa banna tsa praemia. Ka hona, re kholoa hore liphetoho tse teng ho receptor ea DA ho NAcc li ka baka tšebelisano lipakeng tsa bolekane le moputso oa AMPH. Re sebetse likarolo tsa boko ho tsoa lithutong tse sebelisitsoeng litekong tsa CPP bakeng sa DA receptor autoradiographic binding. Tlhahlobo ea ANOVA ea mekhoa e 'meli e bontšitse tšebelisano e kholo lipakeng tsa boiphihlelo ba sechaba (SN kapa PB) le mofuta oa ente (saline kapa AMPH) ho D1R e tlamang ho NAcc (F(1, 29) = 17.63, p <0.01). Teko ea posthoc e senotse hore matšoenyeho a tlamang a D1R ho NAcc ea SN-AMPH le lihlopha tsa PB-saline a ne a ka bapisoa ebile a phahame haholo ho feta a lihlopha tsa SN-saline le PB-AMPH (Setšoantšo sa 3a). Ha ho kalafo ea AMPH kapa boiphihlelo ba bobeli bo fetotseng letsoalo la D2R le tlamang ho NAcc (Setšoantšo sa 3b). Ntle le moo, ha ho liphapang tsa sehlopha tse fumanoeng ho D1R kapa D2R e tlamang ho caudate putamen (datha ha li bonts'itsoe).

Setšoantšo sa 3  

Ho kopana ha Pair le AMPH lia kopana ho ama li-receptor tsa DA. (a) Boemo ba AMPH bo ile ba eketsa botebo ba NAcc D1R e tlamang ho banna ba SN (SN-AMPH), ha ba bapisoa le li-control tsa sindine ea saline (SN-saline). Leha ho le joalo, banna ba PB ba ente ka letsoai ...

NAcc D1R activation mediates moputso oa AMPH ho banna ba SN

Ka li-voes tsa praemia tsa banna, li-entcutaneous injection tsa D1R, empa eseng D2R, mohanyetsi pele litulo tsa maemo tsa AMPH li felisitse CPP e kenyellelitsoeng (AMPH)Liu et al., 2010). Fuoa karolo e thehiloeng ea NAcc DA moputsong oa AMPH ho mefuta e meng ea litoeba (Yokel le Wise, 1975; Kehoe et al., 1996), re fane ka maikutlo a hore ho fihlella D1Rs ho NAcc nakong ea maemo ho bohlokoa bakeng sa li-CPP tse kenyellelitsoeng lipapaling tsa banna tsa SN. Re fumane hore ba batona ba SN ba fumaneng liente tsa "cerebrospinal fluid" (CSF) ka har'a NAcc ba bonts'a AMP e kenyellelitsoeng CPP (t = 2.90, p <0.01) (Setšoantšo sa 4). Leha ho le joalo, tsamaiso ea intra-NAcc ea mohanyetsi oa D1R, SCH 23390, ebang ke tekanyetso e tlase (4 ng / lehlakoreng) kapa e phahameng (100 ng / lehlakoreng) pele ho linako tsa maemo, e felisitse CPP e kenyellelitsoeng (EP)Setšoantšo sa 4). Ka lehlakoreng le leng, tsamaiso ea intra-NAcc ea mohanyetsi oa D2R, eticlopride, ebang ke tlase (4 ng / lehlakoreng; t = 3.25, p <0.01) kapa e phahameng (100 ng / lehlakoreng; t = 2.30, p <0.05), ha ea ka ea thibela CPP e entsoeng ke AMPH (Setšoantšo sa 4). Ha ho phapang e fumanoeng khafetsa ea lifapano tsa likhopo lipakeng tsa liteko tsa pele le tsa kamora sehlopha leha e le sefe, tse bonts'ang ha ho na phello ea kalafo ts'ebetsong ea locomotor (data ha e bontšoe).

Setšoantšo sa 4  

Ho kenya letsoho ha NAcc DA D1-mofuta (D1R) le li-receptors tsa D2-mofuta (D2R) ho AMPH-induction CPP in sex naïve male prairie voles. Lithuto tsohle li amohetse li-AMPH ka linako tsa maemo. Ka le leng la matsatsi a 3 a boemo, 30 min pele ho AMPH ...

Ts'ebetso ea li-D1Rs ho NAcc e thusa CPP e kenyellelitsoeng ho banna ba PB

Boithuto bo fetileng bo bontšitse hore NAcc D1R activation e bohlokoa bakeng sa CPP e kentsoeng ke AMPH le mabifi a ikhethileng, le tšebeliso ea khetho ea molekane e senyehileng li-voles tsa banna prairie (Aragona et al., 2006; Liu et al., 2010). Fuoa karolo ea li-D1Rs ka boits'oaro boo le ho fumana hore NAcc D1R e tlamang e tlase ho banna ba PB-AMPH ho feta ho banna ba PB-saline le SN-AMPH (Setšoantšo sa 3a), re ts'elisitse kelello e fokotsang tšebetso ea D1R ho NAcc e kanna ea ikarabella bakeng sa khaello ea CPP e kenyellelitsoeng ho banna ba PB. Ho etsa tlhahlobo ea maikutlo ana, re ile ra kena liphatlalatsong tsa CSF kapa CSF tse nang le sebaka sa agonist sa D1R kapa sa antagonist ka ho khetheha ho NAcc pele ho e 'ngoe le e' ngoe ea likarolo tse tharo tsa maemo ebe re ea tlhahlobo ea tlhahlobo ea AMP e kenyellelitsoeng CPP. Joalokaha ho ne ho lebelletsoe, banna ba PB ba fumaneng liente tsa CSF ha baa ka ba bontša CPP e kenyellelitsoeng (AMP)Setšoantšo sa 5). Leha ho le joalo, banna ba PB ba fumaneng liente tsa intra-NAcc tsa agonist ea D1R (t = 4.69, p <0.001), empa eseng mohanyetsi, e bontšitse CPP e susumetsoang ke AMPH (Setšoantšo sa 5). Ho ne ho se na liphapang khafetsa ha lifapano tsa likhopo lipakeng tsa tlhahlobo ea pele le ea kamora sehlopha leha e le sefe (ya data ha e bontšoe).

Setšoantšo sa 5  

Ts'ebetso ea tšebetso ea DA D1-mofuta receptor (D1R) ho NAcc e thusa AMP e kenyellelitsoeng CPP ka li-voes tse tlamahantsoeng tsa banna ba tlamang. Lithuto tsohle li ne li kopantsoe 'me li fuoe AMPH ka linako tsa maemo. Ka le leng la matsatsi a 3 a boemo, 30 min pele ho AMPH ...

TŠOHLOA

Boithuto ho batho le mehlala ea liphoofolo li bontšitse kamano e matla lipakeng tsa tšebeliso ea lithethefatsi / tlhekefetso le boitšoaro ba setjhaba (Bacha et al., 2011a). Ka lebaka la karolo ea eona e tsebahalang molokong oa boits'oaro bo susumetsang, tsamaiso ea mesolimbic DA e maemong a bohlokoa a ho buisana ka tšebelisano lipakeng tsa lithethefatsi tsa tlhekefetso le boits'oaro ba sechaba. Re sa tsoa supa hore ho pepesehela khafetsa maqhama a kopantsoeng a AMPH maqhubu a tlamahano ea banna le hore NAcc DA e sebetsa ka sepheo sena (Liu et al., 2010). Thutong e teng hona joale, re bonts'a hore boiphihlelo bo kopanyang bo sitisa CPP e kentsoeng ke AMP le hore sephetho sena se boetse se kenelletsoe ke NAcc DA. Ha li kopantsoe hammoho, lithuto tsena li bonts'a tšebelisano lipakeng tsa bonto le moputso oa AMPH mme li fana ka maikutlo ho karolo ea NAcc DA ho laola lipuisano tse joalo.

Thutong ea hajoale, re sebelisitse paradigm e neng e thehiloe pele ea CPP (Liu et al., 2010; Bacha et al., 2011b) ho etsa lipatlisiso ka litlamorao tsa ho tlamahana ha maqhama ho thepa e ruisang ea AMPH. Re sebelisa poleloana e 'ngoe ea "thepa e nang le moputso" e hlalosang phello ea AMPH maemong a sebaka hobane e re lumella ho bua ka nako e tšoanang likarolo tsa meputso-ho kenyelletsa le hedonics, thuto e kopaneng, le tšusumetso ea (Berridge le Robinson, 2003) - - li bile le ts'usumetso lits'ebetsong tse ka tlas'a maemo a sebaka (Hnasko et al., 2005; White et al., 2005; Cunningham le Patel, 2007), ntle le ho ba khetholla. Liphetho tsa rona li bonts'a hore maemo a AMPH a hlohlelletsa CPP ho SN, empa eseng PB, li-voles tsa banna, mme ka lebaka leo, li fana ka bopaki ba pele bo matla ba hore boiphihlelo ba kopane bo fokotsa thepa e ruisang ea AMPH. Leha ena e le eona feela thuto ea ho etsa lipatlisiso ka litlamorao tsa tlamahano ea bonono litlamong tse khahlisang tsa lithethefatsi tsa tlhekefetso, lithuto tse fetileng li bontšitse hore liphihlelo / mabaka a mang a bophelo a ka boela a ama moputso oa lithethefatsi. Mohlala, likhoto tse holisitsoeng ke li-cohorts tse ngata tsa boithati tse iphelisang ka tlase ho AMPH (Bardo et al., 2001) le cocaine (Schenk et al., 1987) ka makhetlo a mangata ho feta likhoto tse holisitsoeng a le mong. Ka mokhoa o ts'oanang, likhoto tse holisitsoeng tikolohong e ntlafalitsoeng e nang le lintho tse sa tloaelehang le mekhatlo ea boiketlo ea sechaba e iphemisang e fokolang ea AMPH, e tima boitšoaro bo ikemetseng kapele, mme e hloka tekanyetso e phahameng ea AMPH ho khutlisetsa ho batla lithethefatsi ho feta kamoo likhoto li neng li lula li le ling (Bardo et al., 2001; Green le al., 2002; Litepisi et al., 2006; cf, Schenk et al., 1988; Bardo et al., 1995). Ho feta moo, likhoto tsa basali tse koetliselitsoeng ho hatisa cocaine li ile tsa hlahisa likarabo tse fokolang kamora ho ima le kamora ho inkela letsoho (Hecht et al., 1999), ho fana ka tlhahiso ea hore ts'ebetso ea ho hlahisa le liphetoho tse amanang le ts'ebetso ea botona le botšehali li ka fokotsa thepa ea "cocaine" e matlafatsang. Khopolo ena e tšehetsoa hape ke ho fumana hore likhoto tsa boroetsana li rata tikoloho e amanang le koae 'me li ile tsa bontša habonolo hore li na le k'hok'heine ea k'hok'heine ea koaeSeip et al., 2008), athe matamo a kenyang masapo a khethile ka matla tikoloho e amanang le malinyane ho e mong e amanang le cocaine (Mattson et al., 2001). Hammoho, lithuto tsena li bolela hore lintlha tsa kahisano li ka fokotsa thepa e atlehang ea li-psychostimulants. Liphetho tsa rona li holisa liphumano tsena mme li bonts'a hore boiphihlelo bo kopanyang bo sitisa moputso oa AMPH ho li-voes tsa prairie.

Melemo e khotsofatsang ea lithethefatsi tsa psychostimulant tsa tlhekefetso, joalo ka AMPH, li its'etleha ho keketseho e bakoang ke lithethefatsi tokollong ea NAcc DA le ts'ebetsong e latelang ea li-receptors tsa DA (Yokel le Wise, 1975; Di Chiara le Imperato, 1988; Bergman et al., 1990; Kehoe et al., 1996). Ka hona, liphetoho lipakeng tsa e 'ngoe ea lintlha tsena li ka baka litlamorao tsa bolekane bo kopanetsoeng moputsong oa AMPH. Maemo a DA a lokollotsoeng a amana hantle le litlamorao tse ntle tsa lithethefatsi tsa tlhekefetso (Volkow et al., 1999; Drevets et al., 2001; Leyton, 2010) le tokollo ea psychostimulant-e susumetsang ea NAcc DA e fetotsoe ke boiphihlelo ba sechaba maemong a mang (mohlala, ho itšehla thajana bongoaneng: (Kehoe et al., 1996; Kosten et al., 2005), empa eseng ba bang (mohlala, matlo a ruileng a sechaba: (Bardo et al., 1995)). Thutong ea hona joale, kalafo ea AMPH e ile ea eketsa boemo ba DA ea kantle ho naha ho NAcc, e lumellanang le litlaleho tse fetileng (Di Chiara le Imperato, 1988; Curtis le Wang, 2007; McKittrick le Abercrombie, 2007). Ntle le moo, AMPH e bakile ho fokotseha kapele le ka nako e telele ho boemo ba DOPAC ba li-extracellular ka lihlopha tsena ka bobeli. Phumano ena e lumellana le ea lithuto tsa pejana le karolo e tsejoang ea AMPH thibelong ea monoamine oxidase — enthanme e kentseng letsoho ho hlokofatseng ha DA (Green le el Hait, 1978; Jones et al., 1998; Curtis le Wang, 2007). Maemong ana ka bobeli, sebopeho sa boholo le sebopeho sa liphetoho tsa extracellular ho NAcc li ne li bapisoa pakeng tsa banna ba SN le PB, ho fana ka maikutlo a hore ha ho na monyetla oa hore litlamorao tsa ho tlamahana ka moputso oa AMPH li amana le ho lokolloa kapa metabolism ea NAcc DA.

Le ha boiphihlelo bo kopaneng bo sa ka ba susumetsa tokollo ea AMPH kapa e hlahisang metabolism ea AMPH, e bile le tšusumetso litlamorao tsa AMPH ho NAcc DA receptor binding (ke hore, polelo ea receptor ea DA le / kapa tumellano). Mohlala, e lumellanang le lithuto tse fetileng, kalafo ea AMPH e ile ea eketsa polelo ea NAcc D1R ho banna ba SN (Liu et al., 2010) le boiphihlelo bo kopanyang bo boetse bo phahamisitse NAcc D1R e tlamang (Aragona et al., 2006). Leha ho le joalo, phello ea AMPH ho NAcc D1R binding e ile ea khutlisetsoa ho banna ba PB ha e bapisoa le banna ba SN, kaha banna ba PB ba bontšitse ho fokotseha ho hoholo ha D1R ha ho latela kalafo ea AMPH. Ha ho liphapang tsa sehlopha tse fumanoeng NAcc D2R e tlamang ho lithuto tsa hona joale kapa tse fetileng (Aragona et al., 2006; Liu et al., 2010). Ka bobeli lintlha tsena li bonts'a hore boiphihlelo ba kopane le ho pepesetsoa hoa AMPH e 'ngoe le e' ngoe e lebisa ho liphetoho tse ikhethileng tsa D1R kahare ho NAcc ea banna ba SN. Ntle le moo, ha AMPH e amme NACC D1R ka tsela e hanyetsanang libakeng tsa SN le tsa PB, datha ea rona e bonts'a hore tlamahano ea sechaba e ka ba lebaka la bohlokoa lipakeng tsa litlamorao tsa AMPH tsamaisong ea mesolimbic DA. Ka mokhoa o ts'oanang, cocaine e fumanoe e baka phetoho e matla ea mali-oxygen-e itšetlehileng ka boemo ba moea (BOLD) ts'ebetsong eohle ea mesolimbic DA ho basali, empa leha ho le joalo e le karabelo e mpe e BANG ea matamo a lactating, joalo ka ha e lekantsoe ke monahano o sebetsang oa matla a matla a khoheli (Ferris et al., 2005) -Empa e bonts'ang hore boiphihlelo sechabeng / ho tsa thobalano bo ka bapala karolo ea bohlokoa karabelong ea methapo ea kutlo lithethefatsi tsa tlhekefetso. Liphetoho ho li-receptor binding, joalo ka tse hlalositsoeng kaholimo li ka ba le litlamorao tse ngata boits'oarong hobane li fetola karabelo ea boko ho li-neurotransmitters tse lokollotsoeng. Ho banna ba SN, mohlala, keketseho ea AMPH e kenyellelitsoeng ho D1R binding e ka bapala karolo ea bohlokoa nakong ea boemo ba AMPH e le intra-NAcc blockade ea D1R, empa eseng D2R, inhibhibilie e hlahisang AMPH-induction ea CPP-e fumanoang e lumellanang le ea mefuta e meng (Baker et al., 1998; Pitchers et al., 2010). Ka lebaka leo, ho banna ba PB, ho fokotsoa ha NAcc D1R ho ka baka ho haella ha CPP e kenyellelitsoeng e le ts'ebetso ea NAcc D1R nakong ea maemo a AMPH e nolofalletsang AMP e kenyellelitsoeng ke banna ba PB. Ka kopanelo, lintlha tsena li bonts'a hore ho fokotseha ha AMPH-ikiwa ho fokotsehile ho polelo ea NAcc D1R / kamano e ka tlisoang ke litla-morao tsa boiphihlelo ba kopane ka moputso oa AMPH.

Ho tšoanela ho tšoana ho teng lipakeng tsa lintho tseo re li fumaneng le tse tsoang lipatlisisong tse ling tse entseng lipatlisiso mabapi le kamano lipakeng tsa lithethefatsi tsa tlhekefetso le boitšoaro ba sechaba. Taba ea pele, ho tlamahana le ho pepeseha hoa AMPH ka makhetlo a mangata ka boinotšing ho felletse ka liphetoho tse tšoanang tsamaisong ea mesolimbic DA ea li-voes prae tsa banna (ke hore, D1R binding (Aragona et al., 2006) le polelo (Liu et al., 2010) ho NAcc). Ka mokhoa o ts'oanang, boiphihlelo ba thobalano le ho pepesetsoa khafetsa ho psychostimulants e 'ngoe le e' ngoe e matlafalitse letsoalo la methapo ea methapo ho li-spiny neurons tse bohareng kahare ea NAcc ka litoeba (Robinson le Kolb, 1999; Pitchers et al., 2010). Ntle le moo, ho anyesa ho anyesa matamo le tsamaiso ea koae ho basali ba tšehali ho kentse ts'ebetso e ts'oanang ea ts'ebetso e ntle ea BOLD ts'ebetsong ea mesocorticolimbic (Ferris et al., 2005). Hajoale lintlha tsena li tšehetsa taba ea hore lithethefatsi tsa tlhekefetso li nka methapo ea kutlo le mekoloko e arolelanang boitšoaro bo fetohang (Panksepp et al., 2002). Taba ea bobeli, tlhaiso-leseling ea rona e fana ka maikutlo a hore likarabo tse arohaneng tsa neurobiological ho AMPH ho SN le banna ba PB li ka baka karohano ea sehlopha boits'oarong bo susumetsang ba AMPH. Ka mokhoa o ts'oanang, likhoto tse lactating li bonts'itse khatello ea ts'ebetso kahare ho sisteme ea mesocorticolimbic DA ho arabela cocaine (ho fapana le keketseho ea ketsahalo e bonoeng ho basali ba batšehali) (Ferris et al., 2005) le phokotso ea ho itlhokofatsa ka koae (Hecht et al., 1999), e ts'ehetsa le ho feta taba ea hore liphetoho tsa 'mele tse amanang le boiphihlelo ba sechaba li ka hlahisa meputso e khahlisang ea lithethefatsi tsa tlhekefetso.

Ho ba teng ha maqhama a matla sechabeng ho ba batho ba baholo ho ka fokotsa tlokotsi ea tlhekefetso ea lithethefatsi (Kosten et al., 1987). Leha ho le joalo, mekhoa ea neural e tlasa ketsahalo ena ea boits'oaro ha e tsejoe — mohlomong e le ka lebaka la ho haella ha mohlala oa phoofolo e nepahetseng. Thutong e teng hona joale, re thehile mofuta oa phoofolo e le mohlala oa liphoofolo ho etsa lipatlisiso ka mekhoa ea ts'ireletso e tlisoang ke tlamahano ea batho ba baholo ea ho ba tlokotsing ea tlhekefetso ea lithethefatsi. Seo re se fumaneng se bonts'a hore boiphihlelo bo kopane bo fokotsa thepa e ruisang ea AMPH le hore mesolimbic DA sistimi-haholo-holo li-neurotransmission tsa DA ho NAcc-e lumellana le sena. Liphumano tsena, hammoho le tse tsoang lithutong tsa rona tse fetileng (Liu et al., 2010) theha motheo oa lipatlisiso tsa nako e tlang tsa mekhoa ea neural e thehiloeng kamanong ea tšebeliso ea lithethefatsi / tlhekefetso le tlamahano ea sechaba, eo qetellong e ka fanang ka leseli la bohlokoa mabapi le thibelo kapa kalafo ea tlhekefetso ea lithethefatsi.

Liteboho

Re leboha Claudia Lieberwirth, Kelly Lei, Melissa Martin, le Adam Smith ka ho bala ha bona ho thata ho bala sengolo sena se ngotsoeng. Ntle le moo, re leboha Terry E. Robinson ka ho bala sengoloa sa pele sa buka ena le ho fana ka litlhahiso tsa hae tsa bohlokoa. Mosebetsi ona o tšehelitsoe ke National Institutes of Health Grants DAF31-25570 to KAY, HDR01-48462 to JTC, and DAR01-19627, DAK02-23048, and MHR01-58616 to ZXW.

LITLHAHISO

  1. Aragona BJ, Detwiler JM, Wang Z. Amphetamine moputso ka monogamous prairie vole. Neurosci Lett. 2007; 418: 190-194. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  2. Aragona BJ, Liu Y, Curtis JT, Stephan FK, Wang Z. Karolo e mahlonoko ea li-dusamine tsa nucleus accumbens dopamine ka popong ea khetho ea molekane ho li-voes tsa banna tsa prairie. J Neurosci. 2003; 23: 3483-3490. [E fetotsoe]
  3. Aragona BJ, Liu Y, Yu YJ, Curtis JT, Detwiler JM, Insel TR, Wang Z. Nuklea e bokella dopamine ka mokhoa o fapaneng pakeng tsa ho theha le ho boloka litlamo tsa monogamous pair. Nat Neurosci. 2006; 9: 133-139. [E fetotsoe]
  4. Baker DA, Fuchs RA, Specio SE, Khroyan TV, Neisewander JL. Litlamorao tsa tsamaiso ea intraaccumbens ea SCH-23390 mabapi le tšusumetso e mpe ea koae le sebaka se ratoang ke maemo. Synfall. 1998; 30: 181-193. [E fetotsoe]
  5. Bardo MT, Klebaur JE, Valone JM, C. C. Matlotlo a tikoloho a fokotsa ho itšehla thajana ea amphetamine lipakeng tsa basali le banna. Psychopharmacology (Berl) 2001; 155: 278-284. [E fetotsoe]
  6. Bardo MT, Bowling SL, Rowlett JK, Manderscheid P, Buxton ST, Dwoskin LP. Tlhokomelo ea tikoloho e thibela ho hlohlelletsoa ha lits'ebeletso, empa ha e lokolloe ka in vitro dopamine, e bakoang ke amphetamine. Pharmacol Biochem Behav. 1995; 51: 397-405. [E fetotsoe]
  7. Bell NJ, Forthun LF, Sun SW. Khokahano, matla a bocha le tšebeliso ea lithethefatsi: maikutlo a nts'etsopele thutong ea boitšoaro bo kotsing. Sebelisa hampe. 2000; 35: 1177-1206. [E fetotsoe]
  8. Bergman J, Kamien JB, Spealman RD. Khopolo-taba ea ho itaola ka koae ka ho khetha dopamine D (1) le bahanyetsi ba D (2). Behav Pharmacol. 1990; 1: 355-363. [E fetotsoe]
  9. Berridge KC, Robinson TE. Moputso o motle. Mekhoa ea Neurosci. 2003; 26: 507-513. [E fetotsoe]
  10. Brennan KA, Shaver PR. Boholo ba khokahano ea batho ba baholo, bo ama regulation, le kamano ea lerato ea sebetsa. Bulletin ea Botho le Boiketlo ba Sechaba. 1995; 21: 267-283.
  11. Caspers KM, Cadoret RJ, Langbehn D, Yucuis R, Troutman B. Menehelo ea setaele sa khokahanyo le ts'ebeliso ea ts'ehetso ea sechaba ho ts'ebeliso ea nako ea nako ea lintho tse seng molaong. Moemeli oa Behav. 2005; 30: 1007-1011. [E fetotsoe]
  12. Cunningham CL, Patel P. Ho kenella ka mokhoa o potlakileng oa mokhoa oa Pavlovian ho setšoantšo sa ethanol se palangoang ka litoeba. Psychopharmacology (Berl) 2007; 192: 231-241. [E fetotsoe]
  13. Curtis JT, Wang Z. Amphetamine e le litlamorao litorong tsa microtine: Phuputso e bapisoang e sebelisang mefuta e nyarosang le e litšila ea tlholeho. Neuroscience. 2007; 148: 857-866. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  14. Di Chiara G, Mofuthu A. Lithethefatsi tse hlekefetsoeng ke batho li eketsa ka ho khetheha synaptic dopamine tse kenyelletsong ka mokhoa o motlakase oa ho tsamaisa likhoto. Proc Natl Acad Sci US A. 1988; 85: 5274-5278. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  15. Drevets WC, Gautier C, Price JC, Kupfer DJ, Kinahan PE, Mohau AA, Price JL, Mathis CA. Amphetamine-induced dopamine dopamine e hlahisoang ka har'a li-ventral striatum correlates tsa motho tse nang le euphoria. Psychology ea Biol. 2001; 49: 81-96. [E fetotsoe]
  16. Ellickson PL, Collins RL, Bell RM. Tšebeliso ea bongoana ea lithethefatsi tse seng molaong ntle le matekoane: tlamo ea setsoalle e bohlokoa hakae, hona ke ea merabe efe? Sebelisa hampe. 1999; 34: 317-346. [E fetotsoe]
  17. Ferris CF, Kulkarni P, Sullivan JM, Jr, Harder JA, Messenger TL, Febo M. Pup o anya ho feta moputso ho feta koae: bopaki bo tsoang ho ts'ebetso ea ho nahana ka matla a matla a maiketsetso le tlhaiso-leseling ea likarolo tse tharo. J Neurosci. 2005; 25: 149-156. [E fetotsoe]
  18. Fiorino DF, Phillips AG. Ho khothaletsa boitšoaro bo bobe ba thobalano le ho ntlafatsa dopamine efflux mokokotlong oa li-rats ka mor'a hore D-amphetamine e susumelletse boitšoaro bo botle. J Neurosci. 1999; 19: 456-463. [E fetotsoe]
  19. Gingrich B, Liu Y, Cascio C, Wang Z, Insel TR. Li-receptor tsa Dopamine D2 tse bokellaneng tsa li-nucleus li bohlokoa bakeng sa khokahano ea sechaba ho basali ba prairie voles (Microtus ochrogaster) Behav Neurosci. 2000; 114: 173-183. [E fetotsoe]
  20. Green AL, el Hait MA. Thibelo ea "brain brain" monoamine oxidase ka (+) - amphetamine ho vivo. J Pharm Pharmacol. 1978; 30: 262-263. [E fetotsoe]
  21. Green TA, Gehrke BJ, Bardo MT. Phumatso ea tikoloho e fokotsa taolo ea methapo ea methapo ho litheko: ts'ebetso ea karabelo ea tekanyetso bakeng sa litekanyetso tse tsitsitseng le tse tsoelang pele. Psychopharmacology (Berl) 2002; 162: 373-378. [E fetotsoe]
  22. Hecht GS, Spear NE, Spear LP. Liphetoho mabapi le keketseho e ntseng e tsoela pele ea tlhahiso ea koae e kenang kahare ho ts'ebetso ea kemiso ea ratsong ea basali. Dev Psychobiol. 1999; 35: 136-145. [E fetotsoe]
  23. Henry DJ, Greene MA, White FJ. Litholoana tsa motlakase tsa cocaine tsamaisong ea dopamine ea mesoaccumbens: tsamaiso e phetoang. J Theracol Exp Ther. 1989; 251: 833-839. [E fetotsoe]
  24. Hnasko TS, Sotak BN, Palmiter RD. Moputso oa morphine ho litoeba tse haelloang ke dopamine. Tlhaho. 2005; 438: 854-857. [E fetotsoe]
  25. Insel TR, Hulihan TJ. Mokhoa o ikhethileng oa bong ba ho tlama maqhama a mabeli: oxytocin le sebopeho sa khetho ea molekane ho li-voogamous voles. Behav Neurosci. 1995; 109: 782-789. [E fetotsoe]
  26. Jones SR, Gainetdinov RR, Wightman RM, Caron MG. Mekhoa ea ketso ea amphetamine e senotsoe ho litoeba tse haelloang ke transporter ea dopamine. J Neurosci. 1998; 18: 1979-1986. [E fetotsoe]
  27. Kehoe P, Shoemaker WJ, Triano L, Hoffman J, Arons C. Ho ikhetholla a le mong mokokotlong oa neonatal ho hlahisa liphetoho lipakeng tsa boits'oaro le tokollo ea dopamine ea "ventral striatal dopamine" ho mocha ka mor'a phephetso ea amphetamine. Behav Neurosci. 1996; 110: 1435-1444. [E fetotsoe]
  28. Koob GF, Nestler EJ. The neurobiology ea bokhoba ba lithethefatsi. J Neuropsychiatry Clin Neurosci. 1997; 9: 482-497. [E fetotsoe]
  29. Kosten TA, Zhang XY, Kehoe P. Likarabo tsa boitšoaro bo botle le boits'oaro ho koae ho litšoelesa tsa banna ba baholo tse nang le boiphihlelo ba ho khetholoha. J Theracol Exp Ther. 2005; 314: 661-667. [E fetotsoe]
  30. Kosten TR, Jalali B, Steidl JH, Kleber HD. Kamano ea sebopeho sa lenyalo le ts'ebelisano ho khutlisetsa tlhekefetso hape. Am J Juse drug Usecohol. 1987; 13: 387-399. [E fetotsoe]
  31. Leyton M. The neurobiology ea takatso: dopamine le taolo ea maemo a susumetsang le a susumetsang ho batho. Ka: Kringelback ML, Berridge KC, bahlophisi. Monate oa kelello. New York, NY: Oxford University Press, Inc; 2010. maq. 222-243.
  32. Liu Y, Aragona BJ, young KA, Dietz DM, Kabbaj M, Mazei-Robison M, Nestler EJ, Wang Z. Nuklea e bokella dopamine mediates amphetamine-inductionment of infenderment of bonding in a monogamous rodent mefuta. Proc Natl Acad Sci US A. 2010; 107: 1217-1222. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  33. Mattson BJ, Williams S, Rosenblatt JS, Morrell JI. Ho bapisoa le lintlha tse peli tse khothatsang tse khothatsang: malinyane le cocaine nakong eohle ea pelehi. Behav Neurosci. 2001; 115: 683-694. [E fetotsoe]
  34. McKittrick CR, Abercrombie ED. 'Mapa oa Catecholamine ka har'a li-nucleus accumbens: phapang ea basal le amphetamine e tsosang takatso ea norepinephrine le dopamine ka khetla le mantlha. J Neurochem. 2007; 100: 1247-1256. [E fetotsoe]
  35. Nestler EJ. Na ho na le tsela e tloaelehileng ea limolek'hule ea ho lemalla? Nat Neurosci. 2005; 8: 1445-1449. [E fetotsoe]
  36. Panksepp J, Knutson B, Burgdorf J. Karolo ea tsamaiso ea maikutlo a bokooa litlamong: pono ea neuro-ea ho iphetola ha lintho le mofuta o mocha oa 'ho itlaleha' oa liphoofolo. Bokhoba. 2002; 97: 459-469. [E fetotsoe]
  37. Pitchers KK, Balfour ME, Lehman MN, Richtand NM, Yu L, Coolen LM. Neuroplasticity tsamaisong ea mesolimbic e susumetsoang ke moputso oa tlhaho le ho khaotsa ha moputso ka morao ho moo. Psychology ea Biol. 2010; 67: 872-879. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  38. Robinson TE, Becker JB. Ho mamella liphetoho ho bokong le boits'oaro bo hlahisoang ke tsamaiso ea amphetamine e sa foleng: tlhahlobo le tlhahlobo ea mehlala ea liphoofolo tsa amphetamine psychosis. Brain Res. 1986; 396: 157-198. [E fetotsoe]
  39. Robinson TE, Kolb B. Liphetoho ho morphology ea dendrites le dendritic spines ho li-nucleus accumbens le cortex ea pele ho kamora kalafo e phetoa-phetoang le amphetamine kapa cocaine. Eur J Neurosci. 1999; 11: 1598-1604. [E fetotsoe]
  40. Schenk S, Robinson B, Amit Z. Maemo a matlo a hloleha ho ama tsamaiso e ikemetseng ea taolo ea amphetamine. Pharmacol Biochem Behav. 1988; 31: 59-62. [E fetotsoe]
  41. Schenk S, Lacelle G, Gorman K, Amit Z. Cocaine ho itaola ka litekong tse susumetsoang ke maemo a tikoloho: litlamorao bakeng sa etiology ea lithethefatsi. Neurosci Lett. 1987; 81: 227-231. [E fetotsoe]
  42. Seip KM, Pereira M, MP ea Wansaw, Reiss JI, Dziopa EI, Morrell JI. Khothatso ea tšebeliso ea koae nakong ea pelehi ea thipa ea mosali. Psychopharmacology (Berl) 2008; 199: 119-130. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  43. DJ Stairs, Klein ED, Bardo MT. Liphello tsa ho ruisa tikoloho pheletsong le ho khutlisetsong ha phepelo ea amphetamine le karabelo e bolokiloeng. Behav Pharmacol. 2006; 17: 597-604. [E fetotsoe]
  44. E bolokiloe AF, Curtis JT. Amino acid neurotransmitters ho nucleus trus solitarius: boithuto ba tlhahlobo ea vivo. J Neurochem. 1993; 61: 2089-2098. [E fetotsoe]
  45. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Wong C, Hitzemann R, Pappas NR. Matlafatso a matlafatsang a li-psychostimulants ho batho a amahanngoa le ho eketseha ha dopamine ea kelello le ho lula ha li-receptors tsa D (2). J Theracol Exp Ther. 1999; 291: 409-415. [E fetotsoe]
  46. Vungkhanching M, Sher KJ, Jackson KM, Parra GR. Kameho ea tloaelo ea ho ikamahanya le nalane ea lelapa ea lits'ila le ts'ebeliso ea lino tse tahang botsofaling ba pele. Lithethefatsi. 2004; 75: 47-53. [E fetotsoe]
  47. White NM, Chai SC, Hamdani S. Ho ithuta mofuta oa khetho ea morphine e ratoang: tlhophiso ea cue e lekola litlamorao tsa liso. Pharmacol Biochem Behav. 2005; 81: 786-796. [E fetotsoe]
  48. Yokel RA, RA ea Wise. Ho eketsa khatello ea lever bakeng sa amphetamine ka mor'a pimozide ho litoeba: litlamorao bakeng sa khopolo ea dopamine ea moputso. Mahlale. 1975; 187: 547-549. [E fetotsoe]
  49. Young KA, Gobrogge KL, Wang ZX. Karolo ea mesoporticolimbic dopamine ho laola tšebelisano lipakeng tsa lithethefatsi tsa tlhekefetso le boits'oaro ba sechaba. Neurosci Biobehav Rev. 2011a; 35: 498-515. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  50. KA e nyane, Liu Y, Gobrogge KL, Dietz DM, Wang H, Kabbaj M, Wang Z. Amphetamine alters boitšoaro le mesocorticolimbic dopamine receptor expression in the monogamous fem prae vole. Brain Res. 2011b; 1367: 213-222. [Tlhahiso ea mahala ea PMC] [E fetotsoe]