The discriminative stimulus properties of cocaine: effects of BAY K 8644 and nimodipine.
Calcium channel blockers appear to reduce the cardiac toxicity of cocaine and some stimulant-induced behaviors. The present experiment was designed to test whether the internal state induced by cocaine is altered by the calcium antagonist nimodipine. Substitution tests with the calcium agonist BAY K 8644 were also conducted in rats (N = 8) trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced drug discrimination paradigm. Cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding while BAY K 8644 (0.25-2 mg/kg) and nimodipine (0.2-0.8 mg/kg) engendered primarily saline responding. In combination with cocaine (2.5-10 mg/kg), nimodipine shifted the cocaine dose-response curve to the right at doses of 0.2 and 0.4 mg/kg; this attenuation did not increase with higher doses of nimodipine (0.8 and 1.6 mg/kg). The present results suggest that nimodipine may partially block the discriminative stimulus properties of cocaine, however, this reduction is neither robust nor dose-related. Thus, nimodipine might be expected to only marginally alter the subjective cocaine state in humans.
Callahan
P M
PM
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Cunningham
K A
KA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology
D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003042:Cocaine