Isradipine suppresses amphetamine-induced conditioned place preference and locomotor stimulation in the rat

The locomotor activating and the reinforcing effects of psychomotor stimulants are considered to be correlated with and responsible for the development and maintenance of stimulant addiction. Experiments were conducted to examine the effects of isradipine, the L-type calcium channel inhibitor, on the d-amphetamine-induced (1 mg/kg IP) reinforcement (conditioned place preference) and locomotor stimulation. Isradipine dose-dependently (0.6, 1.2, 2.5 mg/kg IP) attenuated the reinforcing effect of amphetamine. Two higher doses completely blocked the induction of place preference. At these doses isradipine also prevented the increase in the number of intercompartment crosses that was observed in both amphetamine- and vehicle-treated controls. In an acute experiment, isradipine failed to affect locomotor activity on its own either in the place preference boxes or in the open field. Amphetamine increased the open field activity but did not change the number of crosses in the place preference boxes. Only the highest (2.5 mg/kg) dose of isradipine significantly suppressed amphetamine-induced hyperactivity in the open field. The present results suggest that isradipine interferes with amphetamine-derived reinforcement at doses lower than those needed to block the acute locomotor effects of amphetamine. Given the qualitatively similar, previously reported results with verapamil, we conclude that the antireinforcing effects of the L-type calcium channel blockers cannot be exclusively explained by the suppression of psychomotor stimulation. The present results further support the notion that the L-type calcium channel blockers may be effective against stimulant addiction.