Regulation of cocaine-reinstated drug-seeking behavior by kappa-opioid receptors in the ventral tegmental area of rats.
Psychopharmacology (Berl)
; 210(2): 179-88, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20232055
ABSTRACT
RATIONALE Relapse is one of the main challenges facing the current treatment of cocaine addiction. Understanding its neurobiological mechanism is a critical step toward developing effective anti-relapse therapies. OBJECTIVES:
Emerging evidence indicates that glutamate-mediated activation of dopamine (DA) neurons in the ventral tegmental area (VTA) may be critically involved in cocaine-induced relapse to drug-seeking behavior. Activity of VTA DA neurons is modulated by multiple neurotransmitter systems including opioids, serotonin, dopamine, and acetylcholine. Recent studies demonstrated that activation of kappa-opioid receptors (kappaORs) in the rat VTA directly inhibits the activity of a subpopulation of DA neurons projecting to the prefrontal cortex (PFC) and amygdala. Because we previously showed that blockade of DA receptors in the dorsal PFC inhibits cocaine-induced reinstatement of extinguished cocaine-seeking behavior suggesting a critical role of the VTA-PFC DA circuit in this process, we tested the hypothesis that activation of kappaORs in the VTA will block cocaine-induced reinstatement in rats.METHODS:
Rats were trained to self-administer intravenous cocaine (0.125 mg/infusion) under a modified fixed-ratio five schedule. After extinction of the learned behavior, the effects of activation of VTA kappaORs on cocaine-induced reinstatement were studied.RESULTS:
The kappaOR agonist U50 488 (0-5.6 microg/side) microinjected into the VTA dose-dependently decreased cocaine-induced reinstatement. The effects could not be explained by either a disruption of operant behavior or diffusion of the drug to the areas surrounding the VTA. Moreover, the effect was reversed by norbinaltorphimine.CONCLUSIONS:
The VTA DA neurons expressing functional kappaORs are critically involved in cocaine-induced reinstatement in rats.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Área Tegmentar Ventral
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Receptores Opioides kappa
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(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida
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Transtornos Relacionados ao Uso de Cocaína
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article