Antagonism of the behavioral effects of cocaine and d-amphetamine by prazosin.
Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1-3.0 mg/kg), cocaine (1.0-3.0 mg/kg) and bupropion (1.0-30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056-0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha 1 antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate-increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha 1 receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016642:Bupropion; D003042:Cocaine / Q000037:antagonists & inhibitors*; D010856:Columbidae; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors*; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D011427:Propiophenones / Q000494:pharmacology; D012453:Saimiri
D011427:Propiophenones; D016642:Bupropion; D003042:Cocaine; D003913:Dextroamphetamine; D011224:Prazosin