ABSTRACT
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.
Subject(s)
Antipsychotic Agents/pharmacology , Behavior, Animal/drug effects , Motor Activity/drug effects , Obsessive-Compulsive Disorder/drug therapy , gamma-Aminobutyric Acid/metabolism , Animals , Antipsychotic Agents/administration & dosage , Baclofen/administration & dosage , Baclofen/pharmacology , Bicuculline/administration & dosage , Bicuculline/pharmacology , Carbamazepine/administration & dosage , Carbamazepine/pharmacology , Dose-Response Relationship, Drug , Lamotrigine , Lithium Carbonate/administration & dosage , Lithium Carbonate/pharmacology , Male , Mice , Mice, Inbred ICR , Muscimol/administration & dosage , Muscimol/pharmacology , Obsessive-Compulsive Disorder/physiopathology , Receptors, GABA-A/drug effects , Triazines/administration & dosage , Triazines/pharmacology , Valproic Acid/administration & dosage , Valproic Acid/pharmacologyABSTRACT
In the present study, we examined the effect of N-acetyl-L-cysteine (NAC), a glutamate-modulating agent, on marble-burying behavior in mice. Fluvoxamine (30 mg/kg, p.o.) and mirtazapine (3 mg/kg, i.p.) significantly inhibited marble-burying behavior without affecting locomotor activity. Similarity, NAC (150 mg/kg, i.p.) significantly inhibited marble-burying behavior without affecting locomotor activity. On the other hand, the antioxidant α-tocopherol (10, 30, and 100 mg/kg, p.o.) had no effect on the marble-burying behavior. These results suggest that the glutamatergic system is involved in the marble-burying behavior, and NAC may be useful for treatment of OCD.
