Selective d‐opioid receptor antagonist N,N(CH 3) 2 ‐Dmt‐Tic‐OH does not reduce ethanol intake in alcohol‐preferring AA rats

Abstract

Abstract We studied the effect of a novel δ‐opioid receptor antagonist N,N(CH 3) 2 Dmt‐Tic‐OH (Me 2 ‐Dmt‐Tic‐OH) on voluntary ethanol intake in an alcohol‐preferring AA (Alko, Alcohol) rat line using a 4‐hour limited access paradigm. Acute injections of Me 2 ‐Dmt‐Tic‐OH (10 and 30 mg/kg, i.p.) did not reduce 1‐hour or 4‐hour ethanol intake. Subtype non‐selective opioid receptor antagonist naltrexone [0.1 and 0.3 mg/kg, subcutaneously (s.c.)] significantly reduced 1‐hour ethanol drinking but had no effect on 4‐hour ethanol consumption. Locomotor stimulation induced by the δ‐opioid receptor agonist Tyr‐D‐Pen‐Gly‐Phe‐D‐Pen (DPDPE; 15 μg, intracerebroventricularly) was significantly attenuated by Me 2 ‐Dmt‐Tic‐OH (10 and 30 mg/kg, i.p.), which confirmed its efficacy as a δ‐opioid receptor antagonist in rat brain. Our results support the idea that δ‐opioid receptors do not mediate alcohol reward in AA rats.