D2 receptor sensitization: Neurobiological basis of increase sensitivity of stress on stimulant induced behavioural sensitization.

Abstract

Abstract Stress is associated with high risk of psychological disorders and cognitive impairment. Psychostimulants are known to enhanced cognition but prolong use causes behavioural sensitization. The locomotor response to psychostimulant potentiated after repeated exposure to stressful stimulus & dopamine play a major role in sensitization-like phenomena. The present study is conducted to visualize responsiveness of dopamine D2 receptors by challenge dose of haloperidol following long term psychostimulant administration in restrained & unrestrained rats. Behavioural Effects of oral methylphenidate (10mg/kg/day 2 times daily) & modafinil (75mg/kg/day once daily) administration in restrained (exposed to immobilization stress for 2 hours daily) and unrestrained rats were monitored for 35 days till the behavioral sensitization produced by using home cage (performed after every two days), open field, Head Dip Test and passive avoidance test (PAT) weekly. The effects of haloperidol challenge dose (1 mg/kg i.p.) were monitored after 35 days of treatment using Home Cage, Open Field, Head Dip and PAT, 30-, 60-, 90- & 120-minutes post injection. The result shows that restrained stress potentiate stimulant-induced behavioural sensitization, produced cognitive deficits and decrease exploratory activity but both stimulants improved cognitive performance and exploratory activity in PAT and head dip test respectively effect was more pronounced in modafinil treated rats. Challenge dose of haloperidol ameliorated motor activity in Home Cage and Open Field, impaired cognition in PAT and decreased activity in head dip test, effect was significant in psychostimulant treated rats but more pronounced in saline treated restrained and psychostimulant treated restrained rats which could be due to supersensitization of D2 receptors that leads to increased sensitivity of stress on stimulant induced behavioural sensitization. This study will help to investigate drugs that could prevent psychostimulant induced behavioural sensitization in stressful environment by understanding of neurobiological basis of the effect of psychostimulants on stress induced motor and cognitive deficits.