title: 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.
authors.affiliation: Sinhgad College of Pharmacy, Pharmacology Division, Vadgaon (Bk), Off Sinhgad Road, Pune 411 041, Maharashtra, India. pra777us@yahoo.com
authors.forename: Pravinkumar
authors.initials: P
authors.lastname: Bhutada
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dixit
authors.forename: Kapil
authors.initials: K
authors.lastname: Thakur
authors.forename: Prashant
authors.initials: P
authors.lastname: Deshmukh
authors.forename: Shyam
authors.initials: S
authors.lastname: Kaulaskar
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000523:psychology; D010879:Piperazines / Q000494:pharmacology*; D044122:Receptor, Melatonin, MT1 / Q000819:agonists; D044123:Receptor, Melatonin, MT2 / Q000819:agonists; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D001640:Bicuculline; D003975:Diazepam; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010879:Piperazines; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes; C015068:1-(3-chlorophenyl)piperazine