Effects of Calcium Channel Entry Blockers on Cocaine-and Amphetamine-Induced Locomotor Activity in Rats

The effects of calcium channel entry blockers (CCEBs) on the spontaneous locomotor activity induced by submaximal and toxic doses of cocaine and amphetamine were determined. Rats were habituated to an automated activity monitor for 30 min, then administered cocaine (0.30-60 mg/kg) or amphetamine (0.04-5 mg/kg), i.p. and data collected for 30 min. CCEBs were administered 30 min prior to the administration of stimulants. Cocaine produced a dose-dependent increase in locomotor activity and stereotypy behavior with a maximum response at 40 mg/kg. Amphetamine produced similar increases in locomotor and stereotypy behavior with a maximum response at 0.6 mg/kg. Nimodipine (5 mg/kg) but not amphetamine (0.3 mg/kg) decreased (p<0.01) cocaine (20 mg/kg)-induced activity and stereotypies. Diltiazem (20 mg/kg) reduced (p<0.01) the stereotypies produced by cocaine but not the cocaine-induced locomotor activity or the stimulant action of amphetamine. Nifedipine (2 mg/kg) inhibited (p<0.05) the stereotypy behavior stimulated by amphetamine (0.3 mg/kg) but not that by cocaine. Nimodipine (5 mg/kg) and nifedipine (2 mg/kg) increased the number of convulsions and lethalities produced by toxic doses of cocaine (40 and 60 mg/kg). The CCEBs also potentiated the toxicity produced by amphetamine (2.5 and 5 mg/kg). The results of this study underscore the variability in the antagonism of the actions of psychomotor stimulants by CCEBs. (Supported by DA 06686)