Antagonism of Cocaine's Reinforcing and Discriminative Stimulus Effects by α-Flupenthixol

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Effects of the D1/D2 dopamine receptor antagonist α-flupenthixol were examined in animal models designed to assess abuse-related behavioral effects of cocaine. Rhesus monkeys (Macaca mulatta) self-administered cocaine (17 or 33 µg/kg/injection, intravenously; IV) during 1-hr daily sessions; periods of food-maintained behavior preceded and followed cocaine access. α-Flupenthixol (0.003–0.03 mg/kg, IV) increased self-administration rates, indicating an antagonism of cocaine's reinforcing effects but decreased rates of food-maintained responding. α-Flupenthixol (0.03 mg/kg) blocked the discriminative stimulus effects of cocaine (0.3 mg/kg) in squirrel monkeys (Saimiri sciureus) but did not do so in rats (Rattus norvegicus) trained to discriminate 10 mg/kg cocaine from saline. On the basis of available animal data and preliminary clinical trials, α-flupenthixol may warrant further study as a cocaine abuse pharmacotherapy.

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