Pharmacological Evidence for a Motivational Role of -Opioid Systems in Ethanol Dependence
Neuropsychopharmacology (2008) 33, 643–652


The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa ()-opioid system has a role in the increased consumption of ethanol in dependent animals.

The effects of three opioid receptor antagonists with different effects on opioid receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats.

The results indicated that both nalmefene and naltrexone induced a significant dose-dependent decrease in the number of lever presses for ethanol in both groups of animals. However, in ethanol-dependent animals, nalmefene was significantly more effective in suppressing ethanol intake than naltrexone. Nor-BNI selectively attenuated ethanol-dependent self-administration while leaving nondependent ethanol self-administration intact. Because naltrexone is primarily selective for the -opioid receptor, and nalmefene is primarily selective for the - and -opioid receptor subtypes, the fact that nalmefene demonstrates more suppression in dependent animals suggests that opioid systems distinct from the -regulated portion may be involved in the increased drinking seen during withdrawal in dependent animals.

The results with nor-BNI confirm that -opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/-opioid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent rats.

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