CONDITIONED TASTE-AVERSION AND PLACE PREFERENCE INDUCED BY THE CALCIUM-CHANNEL ANTAGONIST NIMODIPINE IN RATS

It has become clear that various calcium channel antagonists are able to suppress excessive intake of ethanol in rats. With respect to these findings, it has become of interest whether these drugs can act as re warding and/or aversive stimulus. Therefore, such affective stimulus e ffects of the L-type calcium channel antagonist nimodipine and its ena ntiomers were studied in Wistar rats in a series of conditioned taste aversion (CTA; two-bottle choice procedure) and conditioned place pref erence (CPP; two-compartment procedure) experiments. Racemic nimodipin e (0.95-15 mg/kg IP) was found to induce a dose-dependent CTA, 7.5 mg/ kg being the lowest effective dose. Subsequent studies with both enant iomers revealed that the CTA effects of nimodipine are completely depe ndent on the activity of (-)-nimodipine. With (+)-nimodipine (0.25-90 mg/kg IP), none of the doses tested induced a significant CTA, whereas with (-)-nimodipine clear and dose-dependent CTA effects were noted ( 0.5-30 mg/kg IP). For this enantiomer, the lowest effective dose was 1 5 mg/kg. In additional CPP experiments, it was confirmed that (+)-nimo dipine and (-)-nimodipine have affective stimulus properties, whereas (+)-nimodipine was again an ineffective stimulus (dose used for all dr ugs: 15 mg/kg IP). Interestingly, the affective stimulus effects as me asured with CPP of (+/-)- and (-)-nimodipine turned out to be rewardin g, as it was found that both drugs produced a significant place prefer ence. It is concluded from these studies that nimodipine possesses int rinsic affective stimulus effects which are rewarding in nature. Furth ermore, these stimulus effects are mediated by the activity of the (-) -enantiomer. Possibly, these rewarding effects of nimodipine may play a role in the reported attenuating effects of this drug on voluntary e thanol intake in rats.