Conditioned taste aversion and place preference induced by the calcium channel antagonist nimodipine in rats

Abstract

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 rewarding and/or aversive stimulus. Therefore, such affective stimulus effects of the L-type calcium channel antagonist nimodipine and its enantiomers were studied in Wistar rats in a series of conditioned taste aversion (CTA; two-bottle choice procedure) and conditioned place preference (CPP; two-compartment procedure) experiments. Racemic nimodipine (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 enantiomers revealed that the CTA effects of nimodipine are completely dependent 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 15 mg/kg. In additional CPP experiments, it was confirmed that (±)-nimodipine and (−)-nimodipine have affective stimulus properties, whereas (+)-nimodipine was again an ineffective stimulus (dose used for all drugs: 15 mg/kg IP). Interestingly, the affective stimulus effects as measured with CPP of (±)- and (−)-nimodipine turned out to be rewarding, as it was found that both drugs produced a significant place preference. It is concluded from these studies that nimodipine possesses intrinsic affective stimulus effects which are rewarding in nature. Furthermore, 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 ethanol intake in rats.