Involvement of μ- and δ-opioid receptors in the ethanol-associated place preference in rats exposed to foot shock stress

Abstract

The purpose of this study was to establish the ethanol-induced place preference in rats exposed to foot shock stress using the conditioned place preference paradigm. We also investigated the role of the endogenous opioid system in the development of the ethanol-induced place preference. The administration of ethanol (300 mg/kg, i.p.) with foot shock stress, but not without such stress, induced a marked and significant place preference. Naloxone (1 and 3 mg/kg, s.c.), a non-selective opioid receptor antagonist, significantly attenuated the ethanol-induced place preference. Moreover, the selective μ-opioid receptor antagonist β-funaltrexamine (3 and 10 mg/kg, i.p.) and selective δ-opioid receptor antagonist naltrindole (1 and 3 mg/kg, s.c.), but not the selective κ-opioid receptor antagonist nor-binaltorphimine (1 and 3 mg/kg, i.p.), significantly attenuated the ethanol-induced place preference. Furthermore, 150 mg/kg ethanol (which tended to produce a place preference, although not significantly) combined with each dose (that did not produce a place preference) of the μ-opioid receptor agonist morphine (0.1 mg/kg, s.c.) or selective δ-opioid receptor agonist 2-methyl-4 aα-(3-hydroxyphenyl)-1,2,3,4,4 a,5,12,12 aα-octahydroquinolino [2,3,3- g] isoquinoline (TAN-67; 20 mg/kg, s.c.), but not the selective κ-opioid receptor agonist trans-3,4-dichloro- N-(2-(1-pyrrolidinyl)cyclohexyl)benzenacetamide methanesulfonate (U50,488H; 1 mg/kg, s.c.), produced a significant place preference. These data indicate that stress may be important for development of the rewarding effect of ethanol, and that μ- and δ-opioid receptors may be involved in the rewarding mechanism of ethanol under stressful conditions.