Enhanced sensitivity to the behavioral effects of cocaine after chronic administration of D2-selective dopamine antagonists in the squirrel monkey.
J Pharmacol Exp Ther
; 262(3): 907-15, 1992 Sep.
Article
en En
| MEDLINE
| ID: mdl-1388204
ABSTRACT
The behavioral effects of cocaine (0.03-3.0 mg/kg i.v.) were determined in squirrel monkeys (Saimiri sciureus) trained to respond under a fixed-interval 300-sec schedule of stimulus termination. A session consisted of 13 consecutive fixed-interval components, each followed by a 60-sec timeout. Graded doses of cocaine were injected during selected timeout periods using a cumulative-dosing procedure. Subsequently, two dopamine D2-selective antagonists, spiperone and raclopride, and a D1-selective antagonist, SCH 23390, were administered chronically for a 2-week period. Due to pronounced time course differences, raclopride and SCH 23390 were infused continuously via osmotic minipump, and spiperone was administered i.m. twice per week. Spiperone and raclopride markedly suppressed responding during the 2-week period. When the effects of cocaine were redetermined 3 days after spiperone or 1 day after raclopride administration was terminated, there was a parallel leftward shift in the dose-effect curve, indicating enhanced sensitivity to cocaine. Three days later, sensitivity to cocaine had changed and was similar to that obtained before chronic drug administration. In contrast, SCH 23390 did not alter sensitivity to cocaine after chronic administration was terminated, even though it did attenuate the behavioral effects of cocaine as effectively as spiperone and raclopride. Chronic administration of spiperone did not alter sensitivity to nisoxetine, a norepinephrine uptake inhibitor, or quipazine, a serotonin agonist. The acute administration of spiperone in combination with cocaine also differed markedly from nisoxetine and quipazine. The pronounced rate-decreasing effect of spiperone was attenuated by cocaine in a dose-dependent manner, but not by nisoxetine or quipazine.(ABSTRACT TRUNCATED AT 250 WORDS)
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Base de datos:
MEDLINE
Asunto principal:
Conducta Animal
/
Receptores Dopaminérgicos
/
Cocaína
/
Antagonistas de Dopamina
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
1992
Tipo del documento:
Article