Delta-opioid and 5-HT3 receptor antagonist effects on ethanol reward and discrimination in C57BL/6 mice

The effects of the receptor antagonists MDL 72222 (MDL, 5-HT3) and naltrind ole (delta-opioid) on ethanol reward and its discrimination were examined i n ethanol-preferring C57BL/6 (C57) mice. MDL attenuated lever responding fo r 12% ethanol delivered on a fixed-ratio 8 reinforcement schedule at a dose that did not influence responding for water reward, thus confirming a prev ious report that ICS 205-930 reduced ethanol reward for Long-Evans rats. Ou r study in combination with the reduced ethanol consumption reported for C5 7 mice injected with odansetron indicates that 5-HT3 receptor systems are i nvolved in mediating behavior directed toward obtaining ethanol as well as its consumption. By attenuating the rewarding effects of ethanol or of etha nol conditioned cues (e.g., the operant environment), 5-HT3 antagonists may be useful in the treatment of alcohol abuse. The 5-HT3 antagonist effects in this study are comparable with the effects of naltrexone on ethanol rewa rd in C57 mice, although higher doses were required to reduce operant respo nding for ethanol reward. In contrast to the 5-HT3 antagonist and naltrexon e effects, naltrindole, an antagonist with greater specificity for the delt a-opioid receptor, was without effect on ethanol reward. This result and re cent reports for rats and monkeys suggests that the general antagonists mig ht be more efficacious in attenuating ethanol reward. Both MDL and naltrind ole produced only slight reductions in the ethanol discriminative cue, sugg esting that the rewarding and discriminative effects of ethanol are not lik ely mediated by identical neural mechanisms as previously suggested. (C) 19 99 Elsevier Science Inc.