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Titolo:
DIFFERENTIAL REINFORCING EFFECTS OF COCAINE AND GBR-12909 - BIOCHEMICAL-EVIDENCE FOR DIVERGENT NEUROADAPTIVE CHANGES IN THE MESOLIMBIC DOPAMINERGIC SYSTEM
Autore:
TELLA SR; LADENHEIM B; ANDREWS AM; GOLDBERG SR; CADET JL;
Indirizzi:
GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,3900 RESERVOIR RD NW WASHINGTON DC 20007 NIDA,MOL NEUROPSYCHIAT SECT,NIH BALTIMORE MD 21224 NIDA,BEHAV PHARMACOL & GENET SECT,NIH BALTIMORE MD 21224 NIMH,CLIN SCI LAB BETHESDA MD 20892
Titolo Testata:
The Journal of neuroscience
fascicolo: 23, volume: 16, anno: 1996,
pagine: 7416 - 7427
SICI:
0270-6474(1996)16:23<7416:DREOCA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT NUCLEUS-ACCUMBENS; BIOGENIC-AMINE TRANSPORTERS; H-3 MAZINDOL BINDING; BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; NEUROCHEMICAL CHANGES; WITHDRAWAL; DRUG; SITES; INJECTIONS;
Keywords:
COCAINE; GBR-12909; SELF-ADMINISTRATION; REINFORCING EFFECTS; NEUROADAPTATION; DOPAMINE RECEPTORS; DOPAMINE TRANSPORTERS; DOPAMINE; DRUG ADDICTION; DRUG WITHDRAWAL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
68
Recensione:
Indirizzi per estratti:
Citazione:
S.R. Tella et al., "DIFFERENTIAL REINFORCING EFFECTS OF COCAINE AND GBR-12909 - BIOCHEMICAL-EVIDENCE FOR DIVERGENT NEUROADAPTIVE CHANGES IN THE MESOLIMBIC DOPAMINERGIC SYSTEM", The Journal of neuroscience, 16(23), 1996, pp. 7416-7427

Abstract

The dopamine (DA) transporter is thought to be the primary mediator of reinforcing effects of cocaine. In the present study, an intravenousdrug self-administration procedure, in vitro autoradiography, and HPLC methods were used to investigate possible differences in reinforcingand neuroadaptive responses to cocaine versus GBR-12909, a selective inhibitor of the DA transporter with a postulated therapeutic use in cocaine abuse. Drug-naive rats readily acquired and subsequently maintained cocaine self-administration behavior during 2 hr daily sessions over a prolonged period. In contrast, although GBR-12909 was initially self-administered, both cocaine-naive and cocaine-trained rats failed to maintain self-administration behavior to GBR-12909 over prolonged periods of time. After self-administration responding decreased with GBR-12909, rats showed a delay of 6.6 = 1.3 sessions in reacquiring consistent cocaine self-administration. Moreover, when GBR-12909 was againsubstituted for cocaine, they failed to self-administer GBR-12909, even during the initial days of testing. In contrast, after extinction of self-administration responding by water substitution, rats readily selfadministered both cocaine and GBR-12909. Cocaine self-administration upregulated DA transporters, whereas water-substituted cocaine withdrawal upregulated both DA transporters and D1 receptors. Unlike cocaine. GBR-12909 self-administration by itself altered neither DA transporters nor. D1 or D2 receptors. Nevertheless, substitution of GBR-12909 for cocaine reversed the cocaine-induced upregulation of DA transporters and reduced DA and dihydroxyphenylacetic acid levels in the mesolimbic system. These data suggest that cocaine and GBR-12909 differentially affect dopaminergic systems and also cause different reinforcing and neuroadaptive effects. GBR-12909-like compounds may be useful pharmacotherapeutic agents for cocaine addiction. Upregulation of DA transporters and D1 receptors might play important roles in the neuroadaptivecascade that leads to cocaine addiction and withdrawal.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/21 alle ore 00:13:34