Previous studies have demonstrated that repeated psychostimulant administration produces behavioural sensitization and cognitive tolerance. Brain dopaminergic system and the involvement of dopamine D-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 0.6 mg/kg/day, 2.5 mg/kg/day and 10 mg/kg/day) and modafinil (50 mg/kg/day, 64 mg/kg/day and 75 mg/kg/day) in rats. The effects of challenge dose of haloperidol (at the dose of 1 mg/kg i.p.) has monitored to visualize any subsensitization or supersensitization of D receptors. We found that motor activity and cognitive performance was increased in all doses and sensitization effect was more pronounced after 13 days 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 D receptors which is greater in high dose treated rats. The results show that the role of D 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.

Cognitively impaired PDP showed significantly lower score on visuo-construction and attention. Among all variables of MoCA domains, attention is strongly associated with instrumental activity daily living (IADL) scores (logistic regression coefficient = 0.672, P = 0.01). These results suggest that dementia affects daily living performances especially the IADL tasks like attention and execution. Therefore, the assessment of complex daily activities particularly IADL is probably useful for the diagnosis of early stage cognitive impairment in PDP. Further MMSE test is less sensitive than MoCA for detecting significant cognitive decline in PDP and impaired attention is an important determinant of ADL functions in cognitively impaired PDP.

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Stress is associated with high risk of psychological disorders and cognitive impairment. Psychostimulants are also known to potentiate cognition & ameliorate depression, but their long-term use causes behavioural sensitization. The locomotor response to psychostimulant potentiated after repeated exposure to stressful stimulus & dopamine is thought to 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 repeated administration of methylphenidate (10mg/kg/day 2 times daily) & modafinil (75mg/kg/day once daily) in restrained (exposed to immobilization stress for 2 hours daily) and unrestrained rats were monitored to observe locomotor sensitization, by using familiar environment of home cage (performed after every two days) and novel environment of open field (weekly) however, exploratory activity in Head Dip Test and cognitive activity in passive avoidance test (PAT) were carried out weekly for 35 days (till the behavioral sensitization produced). 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 increase in locomotor activity in drug treated rats potentiated by restrained stress and sensitization effect was significant in 3rd week of psychostimulant administration and was more pronounced in modafinil treated rats. Exploratory activity in Head dip test reduced by restrained stress whereas potentiated by MOD & MPH in unrestrained rats. In restrained rats only MOD prevents stress-induced effect on exploratory behaviour. Restrained stress produced cognitive deficits but MOD and MPH improved cognitive performance in PAT. Challenge dose of haloperidol ameliorated motor activity in familiar and novel environment, impaired cognition in PAT and decreased activity in head dip test, effect was more pronounced in psychostimulant treated restrained mice. This study will be beneficial for the understanding of neurobiological basis of the effect of psychostimulants on stress induced motor and cognitive deficits so helpful to investigate drugs that could prevent psychostimulant induced behavioural sensitization in stressful environment

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.