Effects of agomelatine in a murine model of obsessive–compulsive disorder: Interaction with meta-chlorophenylpiperazine, bicuculline, and diazepam

Abstract

The anticompulsive potential of agomelatine, a potent MT1/2 receptor agonist, and its combined effect with m-chlorophenylpiperazine hydrochloride (mCPP), bicuculline, and diazepam, were investigated in male C57BLJ/6 mice using marble-burying behavior (MBB) test. Acute administration of agomelatine (30–40 mg/kg, intraperitoneal (i.p.)) significantly inhibited the MBB in mice without influencing their locomotor activity. Further, chronic (28 days) administration of lower doses of agomelatine (10 and 20 mg/kg, i.p.) dose-dependently reduced the MBB without influencing their locomotor activity. Interaction studies revealed that pretreatment with mCPP (0.5 mg/kg, i.p.), a serotonin 5HT2C agonist, partially attenuated the anticompulsive effect of agomelatine (30 mg/kg). Further, a GABAA receptor agonist (diazepam, 1.25 mg/kg, i.p.) and antagonist (bicuculline, 1 mg/kg, i.p.) had no influence on the effects of agomelatine on MBB and locomotor activity. The doses of modulators were selected on the basis of dose-response studies. The results indicate that agomelatine has a potent anticompulsive effect that can be attributed to 5HT2C antagonism and MT1/2 agonism, and is certainly not mediated via its effects on the GABAergic system. Thus, the study adds to the growing literature on the psychopharmacological effects of agomelatine, and warrants further exploration in multiple paradigms.

Keywords

• GABAA receptor
• Marble-burying behavior
• Melatonin
• Serotonin