Vol. 287, Issue 1, 284-292, October 1998

Contribution of the Opioid System to Alcohol Aversion and Alcohol Drinking Behavior¹

J. C. Froehlich , N. E. Badia-Elder, R. W. Zink , D. E. McCullough and P. S. Portoghese

Departments of Medicine (J.C.F., N.E.B.-E., R.W.Z., D.E.M.) and Physiology/Biophysics (J.C.F.) and Indiana Program in Medical Neurobiology (J.C.F., R.W.Z.), Indiana University School of Medicine, Indianapolis, Indiana; and Department of Medicinal Chemistry, University of Minnesota College of Pharmacy, Minneapolis, Minnesota (P.S.P.)

The effect of blocking delta opioid receptors on alcohol aversion was examined in female alcohol-preferring (P) rats using a conditioned taste aversion (CTA) paradigm. In experiment 1, alcohol naive P rats were given i.p injections of 0.5, 1.0 or 1.5 g alcohol/kg BW or saline, paired with consumption of a banana-flavored solution during 5 conditioning trials. Alcohol in a dose of 0.5 g/kg was not aversive while the two higher doses (1.0 and 1.5 g/kg) were both aversive in the CTA paradigm. In experiment 2, the effect of the selective delta opioid receptor antagonist, naltrindole (NTI), on alcohol aversion was examined. Rats were pretreated with NTI in doses of 2.5, 5.0, 10.0 or 20.0 mg/kg before conditioning using the nonaversive dose of alcohol from Experiment 1. As in experiment 1, the 0.5 g/kg dose of alcohol did not produce a CTA. Administration of NTI alone in doses of 2.5, 5.0 or 10.0 mg/kg did not produce a CTA. However, when the nonaversive dose of alcohol (0.5 g/kg) was combined with NTI in a dose of either 5.0 or 10.0 mg/kg, an aversion to alcohol was seen. The highest dose of NTI (20 mg/kg) produced a CTA when given either alone and in combination with alcohol. The results indicate that blocking the action of opioid peptides at the delta opioid receptor can make a nonaversive dose of alcohol aversive which suggests that opioid peptides, acting via the delta opioid receptor, play an important role in regulating alcohol aversion.