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Titolo:
Behavioral and neurochemical effects of the dopamine transporter ligand 4-chlorobenztropine alone and in combination with cocaine in vivo
Autore:
Tolliver, BK; Newman, AH; Katz, JL; Ho, LB; Fox, LM; Hsu, K; Berger, SP;
Indirizzi:
Univ,Calif San Francisco, Vet Affairs Med Ctr, Dept Psychiat, San Francisco Univ Calif San Francisco San Francisco CA USA 94121 ychiat, San Francisco NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD USA NIDA Baltimore MD USA ct, Intramural Res Program, NIH, Baltimore, MD USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 1, volume: 289, anno: 1999,
pagine: 110 - 122
SICI:
0022-3565(199904)289:1<110:BANEOT>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
BIOGENIC-AMINE TRANSPORTERS; INDUCED LOCOMOTOR-ACTIVITY; UPTAKE INHIBITORS; NONHUMAN-PRIMATES; NUCLEUS-ACCUMBENS; BINDING-SITES; EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; RAT STRIATUM; GBR-12909;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Tolliver, BK Univentlif San Francisco, Vet Affairs Med Ctr, Dept Psychiat,127,4150 Clem Univ Calif San Francisco 127,4150 Clement St San Francisco CA USA 94121
Citazione:
B.K. Tolliver et al., "Behavioral and neurochemical effects of the dopamine transporter ligand 4-chlorobenztropine alone and in combination with cocaine in vivo", J PHARM EXP, 289(1), 1999, pp. 110-122

Abstract

The current studies evaluated the novel diphenylmethoxytropane analog 4-chlorobenztropine (4-Cl-BZT), cocaine, and combinations of the two drugs for their abilities to stimulate locomotor activity, produce cocaine-like discriminative stimulus effects, and elevate extracellular dopamine (DA) in the nucleus accumbens (NAc) as measured by in vivo microdialysis. Peripherally administered cocaine was approximately twice as efficacious as 4-Cl-BZT as a locomotor stimulant and was behaviorally active at a lower dose than was 4-Cl-BZT. Cocaine also was more efficacious than 4-Cl-BZT in producing discriminative-stimulus effects in rats trained to discriminate i.p. injectionsof 10 mg/kg cocaine from saline. The time course of behavioral activation differed markedly between the two drugs, with much shorter onset and duration of locomotor stimulant effects for cocaine relative to 4-Cl-BZT. Similarly, i.p. cocaine (10 and 40 mg/kg) induced a pronounced, rapid, and short-lived increase in DA in the NAc, whereas i.p, 4-Cl-BZT was effective only atthe higher dose and produced a more gradual, modest, and sustained (greater than or equal to 2 h) elevation in accumbens DA. In contrast to i.p. administration, local infusion of 4-Cl-BZT (1-100 mu M) into the NAc through the microdialysis probe elevated extracellular DA to a much greater extent than did local cocaine (nearly 2000% of baseline maximally for 4-Cl-BZT versus 400% of baseline for cocaine) and displayed a much longer duration of action than cocaine. However, when microinjected bilaterally into the NAc at 30 or 300 nmol/side, cocaine remained a more efficacious locomotor stimulantthan 4-Cl-BZT. Finally, pretreatment with i.p. 4-Cl-BZT dose dependently enhanced the locomotor stimulant, discriminative stimulus effects, and NAc DA response to a subsequent low-dose i.p. cocaine challenge. The diphenylmethoxytropane analog also facilitated the emergence of stereotyped behavior and convulsions induced by high-dose cocaine. The current results demonstrate that DA transporter ligands that do not share the neurochemical and behavioral profiles of cocaine nevertheless may enhance the effects of cocaine in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 07:33:09