Perospirone, a Novel Antipsychotic Drug, Inhibits Marble-Burying Behavior via 5-HT_1A Receptor in Mice: Implications for Obsessive-Compulsive Disorder

Abstract

Perospirone is a novel atypical antipsychotic drug with dopamine (DA) D₂- and serotonin (5-hydroxytryptamine, 5-HT) 5-HT_2A-receptor antagonist, and 5-HT_1A-receptor agonist properties. In the present study, we examined the effect of perospirone on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder (OCD), compared with the effects of other antipsychotics such as haloperidol and risperidone. Perospirone at a dose of 10 mg/kg (p.o.) inhibited marble-burying behavior without affecting the locomotor activity in mice. On the other hand, haloperidol (0.1 mg/kg, i.p.) and risperidone (1 mg/kg, p.o.) showed significant suppression of locomotor activity at the dose that inhibited marble-burying behavior. Furthermore, the inhibition of marble-burying behavior by perospirone was antagonized by WAY100135 (10 mg/kg, i.p.), a selective 5-HT_1A-receptor antagonist. WAY100135 at the same dose also antagonized the inhibition of marble-burying behavior by 8-OH-DPAT (3 mg/kg, i.p.), a selective 5-HT_1A-receptor agonist. These findings suggest that perospirone may exhibit anti-OCD activity in clinical use and that 5-HT_1A-receptor agonistic activity may be involved in the inhibition of marble-burying behavior by perospirone.