COMPARISON OF THE STIMULUS PROPERTIES OF ETHANOL AND THE CA2+ CHANNELANTAGONIST NIMODIPINE IN RATS

A variety of L-type Ca2+ channel antagonists, including the dihydropyr idine derivative nimodipine, have been shown to be effective in reduci ng ethanol intake and preference in animal models of alcoholism. The b ehavioral mechanism involved in the anti-alcohol effects of nimodipine are, however, not clear yet. The aim of the present study was to inve stigate the possibility that the effects of nimodipine on ethanol inta ke are based on stimulus substitution. Therefore, rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg i.p.) from saline in a tw o-lever food-reinforced drug discrimination procedure (dose range of e thanol tested: 125-1000 mg/kg i.p., ED(50) value: 488 mg/kg). In cross -generalization tests with nimodipine (0.15-15 mg/kg i.p.), stimulus s ubstitution was not noted. In addition, a cross-familiarization condit ioned taste aversion paradigm was utilized. In rats, 1000 mg/kg i.p. e thanol was used as the reference drug producing a conditioned taste av ersion. Effects of preexposure to ethanol (500-1500 mg/kg i.p.) and ni modipine (7.5-30 mg/kg i.p.) on the magnitude of the ethanol-induced c onditioned taste aversion were investigated as an index for stimulus s imilarity between preexposure and reference drug. Preexposure to both ethanol and nimodipine prevented the development of a conditioned tast e aversion. Contrary to the drug discrimination results, these latter findings suggest that there may be similarities between the stimulus p roperties of nimodipine and ethanol. Moreover, the apparent discrepanc y between the results obtained in drug discrimination and cross-famili arization conditioned taste aversion suggests that different stimulus properties of ethanol control behavior in both procedures. The finding that, under particular conditions, ethanol and nimodipine appear to s hare common stimulus properties needs to be further evaluated, as this may be related to the reported anti-alcohol effects of nimodipine and other Ca2+ channel antagonists.