TY - JOUR
T1 - The discriminative stimulus properties of cocaine
T2 - effects of BAY K 8644 and nimodipine
AU - Callahan, Patrick M.
AU - Cunningham, Kathryn A.
N1 - Funding Information:
Support for this research was provided by Miles Institute for Preclinical Pharmacological Research and the National Institute on Drug Abuse DA05708. We wish to thank Miles Pharmaceuticals for their generous gifts of BAY K 8644 and nimodipine. We also extend our thanks to Rosalba Luna for her assistance in preparing this manuscript.
PY - 1990/9/4
Y1 - 1990/9/4
N2 - 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.
AB - 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.
KW - (rat)
KW - Behaviour
KW - Ca channel antagonists
KW - Cocaine
KW - Drug discrimination
KW - Nimodipine
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U2 - 10.1016/0014-2999(90)94072-6
DO - 10.1016/0014-2999(90)94072-6
M3 - Article
C2 - 1704310
AN - SCOPUS:0025040043
SN - 0014-2999
VL - 186
SP - 143
EP - 147
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -