Effects of mood stabilizers on marble-burying behavior in mice: Involvement of GABAergic system

Rationale 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. Objectives 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. Methods The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated. Results Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA A receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABA B receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABA A receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg). Conclusions 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.