Effect of haloperidol on behavioral sensitization and cognition in methylphenidate and buspirone-methylphenidate co-administered rats

Abstract

Attenuation of methylphenidate-induced behavioral sensitization and cognitive tolerance by buspirone coadministration has been reported previously. Dopamine D2-receptors are considered to be important in methylphenidateinduced sensitization. This study was designed to monitor the responsiveness of D2 receptors following long-term methylphenidate, buspirone and their co-administration in rats by the challenge dose of haloperidol. Effects of haloperidol challenge dose (1 mg/kg i.p.) were monitored after 6 weeks (till the behavioral sensitization produced) from oral repeated (twice a day for 6 week) administration of methylphenidate (2mg/kg/day), buspirone (10mg/kg/day) and their co-administration. Motor activity was compared by using familiar environment of home cage and novel environment of open field and cognitive activity was compared by using water maze were monitored 30, 60, and 90 minutes post injection respectively. We found that haloperidol reduced motor activity in familiar as well as in novel environment and showed impaired cognitive performance in water maze. The effects were more pronounced in methylphenidate treated rats as compared to buspirone and methylphenidate co-administration treated rats. Increased response of haloperidol in methylphenidate treated rats can be explained in terms of super-sensitization of D2 receptors, which results in behavioral sensitization that is not observed in co-administration treated rats. Buspirone prevents D2 receptor’s super-sensitization by increasing serotonergic inhibitory influence on dopamine neuron.