Effects of mood stabilizers on marble-burying behavior in mice

Abstract

Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD. In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior. The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated. Valproate (10, 30 and 100mg/kg, i.p.) and carbamazepine (30 and 100mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA(A) receptor agonist muscimol (1mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABA(B) receptor agonist baclofen (3mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABA(A) receptor antagonist bicuculline (3mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1mg/kg) and valproate (100mg/kg). These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABA(A) receptor-dependent mechanism.