The effects of amperozide on cocaine-induced social withdrawal in rats.

Cocaine decreases social interactions in both humans and animals, but it is not known whether the drugged animal withdraws from an undrugged conspecific, the undrugged conspecific avoids the drugged animal, or a combination of these two factors occurs. In the first experiment, the source of cocaine-induced social withdrawal was determined using a tether paradigm, in which the movement of one of the rats was restricted to one half of the observation chamber, such that the freely moving rat had the option of escaping social interactions. There were decreases in social interactions in the condition in which both rats were freely moving, and in the condition in which the undrugged rat was tethered, but not when the drugged rat was tethered and could not escape social contact. A second experiment was conducted to test the efficacy of the potent serotonin receptor antagonist, amperozide, in attenuating cocaine-induced social withdrawal using the condition in which the drugged rat was freely moving. Either amperozide (1.0, 3.0, and 5.0 mg/kg) or saline vehicle was injected into rats 1 h before receiving a 30.0 mg/kg cocaine dose. Cocaine decreased social interactions. Amperozide restored social interactions to near control levels and elevated social interactions in the animals treated with saline vehicle.