Antiaggressive and motor effects of haloperidol show different temporal patterns in the development of tolerance.

The study of the temporal course of tolerance development was used as a means to separate different aspects of the action of haloperidol on social behavior. Agonistic behavior was studied in isolated male mice that confronted standard opponents (anosmic and grouped conspecifics) in a neutral area. The aggressive and motor behaviors of the experimental animals were evaluated 30 min or 24 h either after a single injection of haloperidol (0.4 mg/kg) or following the last of a series of 15 or 30 injections. When animals were evaluated 30 min after the haloperidol injection, no tolerance to the antiaggressive effects was evident. The action on immobility, on the contrary, showed a clear tolerance development with repeated drug administration, both with 15 and 30 injections. When evaluated 24 h after the last injection, tolerance to the antiaggressive effects developed with repeated injections. Increased immobility was never found in the tests carried out after 24 h, not even in the single injection group. The clear divergence found in the temporal courses of tolerance to haloperidol in its antiaggressive and motor effects suggests that these actions are mediated through different neurophysiological mechanisms. A parallel with extrapyramidal and therapeutic effects is discussed.