Assessment of Dextromethorphan on Compulsive Behavior Using the Schedule-Induced Polydipsia Paradigm in Rats

Abstract ID 27875 Poster Board 112 Dextromethorphan (DM) is a sigma1 receptor agonist, 5-HT2A receptor agonist, and NMDA receptor antagonist FDA-approved for pseudobulbar affect and, in combination with the dopamine reuptake inhibitor bupropion, for the treatment of major depressive disorder. Antidepressant drugs that exhibit pharmacological actions similar to DM can attenuate symptoms of obsessive-compulsive disorder. The present study aimed to evaluate the effects of DM in rats using the schedule-induced polydipsia procedure, a model of compulsive behavior. In this paradigm, food-, but not water-, restricted animals drink excessive amounts of water when food is delivered on a fixed schedule. This study examined male Wistar rats (food restricted to 85% of free-feed weights) during 60 min sessions with fixed-time 60 second schedules and free access water. Following 20 consecutive daily training sessions, rats were divided into high or low drinker groups. DM (15.0 - 60.0 mg/kg) dose-dependently reduced water consumption and frequency of licks in both the low and high drinker groups. DM reduced food-receptacle head entries in only the low drinker group. Further, the 5-HT2A/2C agonist DOI (0.5 - 2.0 mg/kg) also inhibited water consumption in both low and high drinkers and reduced frequency of head entries in only the low drinker group. Based on these findings, DM may be effective for treating compulsive behavioral disorders and these effects may be facilitated by activation of 5-HT2A receptors. ▪