The antipsychotic trifluoperazine reduces marble-burying behavior in mice via D2 and 5-HT2A receptors: Implications for obsessive-compulsive disorder

Abstract

Trifluoperazine, a typical antipsychotic drug, not only antagonizes dopamine D₂ receptors but also enhances serotonin 5-HT₂ receptor-mediated behavior. Moreover, trifluoperazine suppresses human purinergic receptor P2X7 responses and calmodulin. However, the effect of trifluoperazine on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder (OCD), has not been studied. Here, we examined the effect of trifluoperazine on marble-burying behavior in mice. Oral administration of paroxetine, a selective serotonin reuptake inhibitor, significantly reduced marble-burying behavior without affecting total locomotor activity. Similar results were obtained for trifluoperazine (3mg/kg). The D₂ receptor agonist, quinpirole (0.03mg/kg, intraperitoneal [i.p.]), and 5-HT_2A receptor antagonist, ketanserin (0.3mg/kg, i.p.), significantly counteracted this reduction of marble-burying behavior by trifluoperazine. These results show that trifluoperazine reduces marble-burying behavior via D₂ and 5-HT_2A receptors, and may be a useful drug for the treatment of OCD.

Keywords: Marble-burying behavior; Obsessive–compulsive disorder; Trifluoperazine.