Expression of morphine-conditioned hyperactivity is attenuated by naloxone and pimozide

The present experiments assessed whether morphine-conditioned hyperactivity could be attenuated by either the opiate antagonist naloxone or the dopamine antagonist pimozide. Both of these antagonists were shown to block the unconditioned hyperactivity induced by 2 mg/kg morphine (Experiment 1). Rats were then conditioned by pairing this dose of morphine repeatedly with a distinctive environment (Experiment 2). Following several drug-environment pairings, rats displayed a hyperactive conditioned response (CR) when exposed to the environment in the absence of the drug. CR expression was counteracted by 1 mg/kg naloxone and was attenuated by pimozide (0.25, 0.33, and 0.4 mg/kg) in a dose-related manner. These findings suggest that the unconditioned and conditioned hyperactive responses produced by morphine may involve similar neuropharmacologic substrates.