Modulation of cocaine intravenous self-administration in drug-naive animals by dihydropyridine Ca2+ channel modulators

The dihydropyridine Ca2+ channel blocker nimodipine and the dihydropyridine Ca2+ channel activator BayK 8644 (1,4-dihydropyridine-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-py ridine- 5-carboxylate) were administered to drug-naive mice and rats that were tested for intravenous cocaine self-administration. A range of cocaine doses was tested to investigate the nature of the effect. The results indicate that nimodipine and BayK 8644 shifted the dose-response curve for cocaine's reinforcing action to the right and left, respectively. Thus, the Ca2+ channel blocker nimodipine decreases the sensitivity of mice and rats to the reinforcing effects of cocaine while the Ca2+ channel activator BayK 8644 makes the animals more sensitive to cocaine reward. The results suggest that a dihydropyridine-sensitive mechanism is implicated in the initiation of cocaine self-administration.