The effects of the receptor antagonists
MDL 72222 (MDL, 5-HT3) and
naltrindole (delta-
opioid) on
ethanol reward and its discrimination were examined in
ethanol-preferring C57BL/6 (C57) mice. MDL attenuated lever responding for 12%
ethanol delivered on a fixed-ratio 8 reinforcement schedule at a dose that did not influence responding for water reward, thus confirming a previous report that
ICS 205-930 reduced
ethanol reward for Long-Evans rats. Our study in combination with the reduced
ethanol consumption reported for C57 mice injected with odansetron indicates that
5-HT3 receptor systems are involved in mediating behavior directed toward obtaining
ethanol as well as its consumption. By attenuating the rewarding effects of
ethanol or of
ethanol 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 reward in C57 mice, although higher doses were required to reduce operant responding for
ethanol reward. In contrast to the
5-HT3 antagonist and
naltrexone effects,
naltrindole, an antagonist with greater specificity for the
delta-opioid receptor, was without effect on
ethanol reward. This result and recent reports for rats and monkeys suggests that the general antagonists might be more efficacious in attenuating
ethanol reward. Both MDL and
naltrindole produced only slight reductions in the
ethanol discriminative cue, suggesting that the rewarding and discriminative effects of
ethanol are not likely mediated by identical neural mechanisms as previously suggested.