Haloperidol attenuates Methylphenidate and Modafinil induced behavioural sensitization and cognitive enhancement.

Abstract

Previous studies have demonstrated that repeated psychostimulant administration produces behavioural sensitization and cognitive tolerance. Brain dopaminergic system and the involvement of dopamine D2-receptors are considered to be important in psychostimulant-induced sensitization. Study designed to compared the motor activity by using familiar and novel enviroments and cognitive effects by water maze and passive avoidance test after long term administration of methylphenidate(at the dose 0.6mg/kg/day, 2.5mg/kg/day and 10mg/kg/day) and modafinil (50mg/kg/day, 64mg/kg/day and 75mg/kg/day) in rats. The effects of challenge dose of haloperidol (at the dose of 1mg/kg i.p.) has monitored to visualize any subsensitization or supersensitization of D2 receptors. We found that motor activity and cognitive performance was increased in all doses and sensitization effect was more pronounced after 13days of drug administration were greater at high than low and medium doses.Challenge dose of haloperidol attenuate motor activity in familiar and novel environment and impaired cognition in water maze and passive avoidance test in all treated rats. The effect of Haloperidol in high dose treated rats were however somewhat greater than low and medium dose treated rats following methylphenidate and modafinil administration. Increased response of haloperidol in methylphenidate treated rats can be explained in term of supersensitization of D2 receptors which is greater in high dose treated rats. The results show that the role of D2 receptors to develop side effects such as behavioural sensitization and cognitive tolerance by the long term administration of psychostimulants is of sufficient importance and helpful in understanding the mechanisms underlying the undesirable effects of psychostimulants.