The effect of mGluR5 antagonists on quinpirole-induced compulsive checking behavior in rats

OBJECTIVE: Obsessive-compulsive disorder is higly disabling and decreases quality of life. There are some evident that glutamatergic hyperactivation may play a role in etiology of obsessive-compulsive disorder. Especially, Group I mGluR antagonists, of which their effects was shown anxiolytic-like effects may have any effects on treatment of obsessive-compulsive disorder. In this study, it was aimed to determine the effect of 2-methyl-6-(phenylethynyl)- pyridine (MPEP), Group I mGlu5R antagonist, on D2/D3 agonist quinpirol-induced compulsive checking behavior in rats.METHODS: Kinpirol was injected subcutaneously (0.5 mg/kg, twice weekly x 10). Before fifteen minutes ago, MPEP was injected intraperitoneally (1 mg/kg and 5 mg/kg). Citalopram (10 mg/kg) as active comparator and saline were used for control injection. The behaviors of rats were tracked automatically by Ethovision 7.0 system for 55 minutes in the aim of evaluating compulsive control behavior.RESULTS: MPEP at a dose of 5 mg/kg decreased quinpirol-induced compulsive control behavior but not with 1 mg/kg.CONCLUSION: The results of this study support previous preclinical evident related to mGluR antagonistic control on dopaminergic neurotransmission at basal ganglia especially. This class of drug may be promising agent for treatment of obsessive compulsive disorder in future.Key Words: Obsessive-compulsive disorder, rats, compulsive control, quinpirol, MPEP