Anxiolytic-Like Effects of Perospirone, a Novel Serotonin-2 and Dopamine-2 Antagonist (SDA)-Type Antipsychotic Agent

We examined the anxiolytic potential of perospirone, a novel serotonin-2 and dopamine-2 antagonist (SDA)-type antipsychotic agent, and compared its effects with those of the standard anxiolytic diazepam and the conventional antipsychotic haloperidol by using conditioned defensive burying (CDB) and social interaction (SI) tests in rats. The tests were conducted 1 h after oral administration of the drug. Diazepam inhibited CDB specifically directed toward a probe previously associated with brief electric shock and increased the time spent in SI by pairs of naive rats in a brightly illuminated novel environment. Perospirone mimicked the effects of diazepam by dose dependently suppressing CDB and facilitating SI. In contrast, haloperidol failed to inhibit CDB or increase SI. Thses results suggested that, unlike the conventional antipsychotic haloperidol, perospirone exerts anxiolytic-like effects in animal models with different motivational and emotional states. A braoder efficacy of perospirone for the treatment of anxiety and related symptoms in schizophrenia is discussed.