Inhibition of kappa opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine.

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Wee S, Orio L, Ghirmai S, Cashman JR, Koob GF

Inhibition of kappa opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine.

Psychopharmacology (Berl). 2009 Sep;205(4):565-75. doi: 10.1007/s00213-009-1563-y. Epub 2009 May 30.

PubMed ID

19484223 [ View in PubMed

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Abstract

OBJECTIVE: Previous studies demonstrated that the dynorphin/kappa opioid system was up-regulated upon repeated cocaine self-administration. In the present study, we tested the hypothesis that increased cocaine self-administration with extended access was associated with increased activity of the kappa opioid system in rats. MATERIALS AND METHODS: Rats self-administered 0.5 mg/kg per injection of cocaine on a fixed-ratio (FR) schedule in either 1-h (short access, ShA) or 6-h (long access, LgA) sessions. After cocaine intake in the LgA rats increased to a maximum, the effects of kappa opioid receptor antagonists and a partial agonist were tested on cocaine intake in ShA and LgA rats. RESULTS: Cocaine self-administration increased under FR and progressive-ratio (PR) schedules in LgA rats. Nor-BNI (15-30 mg/kg), a kappa receptor antagonist, decreased cocaine intake in LgA rats under a PR schedule (ShA, +1.7%; LgA, -27.4% from baseline), whereas naltrexone (0.3-10 mg/kg) and SG-II-49 (0.025-0.1 mg/kg), a nonspecific opioid receptor antagonist and a partial agonist, respectively, decreased cocaine intake in both groups (PR data: SG-II-49, ShA -28.6%, LgA -19.8%; naltrexone, ShA -34.6%, LgA -11.8% compared with vehicle data). CONCLUSIONS: The present study demonstrated that the antagonism of kappa opioid receptors attenuated only the increased cocaine intake in LgA rats under a PR schedule, whereas the antagonism of micro and kappa receptors decreased cocaine intake in both ShA and LgA groups. The data suggest that increased motivation for cocaine in rats with extended access may be related to increased kappa opioid activity and may contribute to compulsive use.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Naltrexone	Kappa-type opioid receptor	Protein	Humans	Yes	Antagonist	Details