Calcium channel blockers antagonize some of cocaine's cardiovascular effects, but fail to alter cocaine's behavioral effects.
The effects of cocaine alone and in combination with the calcium channel blockers nimodipine, verapamil and diltiazem were determined for different groups of squirrel monkeys on cardiovascular function, schedule-controlled behavior and drug self-administration. Cocaine alone (0.3 mg/kg) produced increases in both blood pressure and heart rate. All three calcium channel blockers antagonized the pressor effect, but were ineffective against the tachycardiac effect of cocaine. Nimodipine was the most potent agent in antagonizing the pressor effect of cocaine. Response rates for monkeys responding on a second-order schedule of food presentation were increased by intermediate doses of cocaine (0.1-1.0 mg/kg) and were primarily decreased at a higher dose (3.0 mg/kg). Quarter-life values, an index of response patterning, were only decreased by cocaine. None of the calcium channel blockers altered cocaine's effects on either response rate or response patterning. In the self-administration experiments, the training dose of 56 micrograms/kg cocaine maintained high rates of responding on a simple fixed-ratio schedule. As with schedule-controlled behavior, none of the calcium channel blockers altered cocaine self-administration even when administered before self-administration sessions during 5 consecutive days. These results suggest that the calcium channel blockers may be useful in treating cardiovascular-related complications after cocaine use, but they would not be effective as long-term treatment agents for cocaine abuse.
Preclinical Pharmacology Laboratory, Addiction Research Center, Baltimore, Maryland.
C W
CW
Schindler
S R
SR
Tella
J
J
Prada
S R
SR
Goldberg
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D012453:Saimiri; D012646:Self Administration; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009553:Nimodipine; D014700:Verapamil; D004110:Diltiazem; D003042:Cocaine