Roles of 5-HT3 and opioid receptors in the ethanol-induced place preference in rats exposed to conditioned fear stress

The effect of the selective 5-HT3 receptor antagonist ondansetron on the et hanol-induced place preference in rats exposed to conditioned fear stress, which stimulates the release of endogenous opioid peptides (beta-endorphin auld enkephalins), was investigated using the conditioned place preference paradigm. In addition, we also examined the effect of ondansetron on the et hanol-induced place preference enhanced by the administration of mu- and de lta-opioid receptor agonists (exogenous opioids). The administration of eth anol (300 mg/kg, i.p.) induced a significant place preference in rats expos ed to conditioned fear stress. Pretreatment with ondansetron (0.01 and 0.1 mg/kg, s.c.) effectively attenuated this ethanol-induced place preference. When the mu-opioid receptor agonist morphine (0.1 mg/kg, s.c.) or the: sele ctive delta-opioid receptor agonist 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2 ,3,4,4a,5,12,12a alpha-octahydroquinolino [2,3,3-g] isoquinoline (TAN-67; 2 0 mg/kg, s.c.) was administered in combination with 75 mg/kg ethanol (which tended to produce a place preference), the ethanol-induced place preferenc e was significantly enhanced. The selective mu-opioid receptor antagonist b eta-funaltrexamine at a dose of 10 mg/kg significantly attenuated the enhan cement of the ethanol-induced place preference produced by morphine. Ondans etron (0.1 mg/kg, s.c.) also significantly attenuated the enhancement of th e ethanol-induced place preference produced by morphine. Furthermore, the s elective delta-opioid receptor antagonist naltrindole at a dose of 3 mg/kg significantly attenuated the enhancement of the ethanol-induced place prefe rence produced by TAN-67. Ondansetron (0.1 mg/kg, s.c.) slightly, but signi ficantly, attenuated the enhancement of the ethanol-induced place preferenc e produced by TAN-67. These results suggest that 5-HT3 receptors may be inv olved in the rewarding mechanism of ethanol under psychological stress, and may play an important role in the rewarding effect of ethanol through the activation of mu- and delta-opioid receptors. (C) 1999 Elsevier Science Inc .