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Haloperidol attenuates Methylphenidate and Modafinil induced behavioural sensitization and cognitive enhancement

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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 0.6 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 D2 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 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.

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Fig. 1: Effect of Methylphenidate administration on motor activity in familiar environment.
Fig. 2: Effect of challenge dose of Haloperidol in Methylphenidate treated rats on motor activity in familiar environment.
Fig. 3: Effect of Methylphenidate administration on motor activity in novel environment.
Fig. 4: Effect of challenge dose of Haloperidol in Methylphenidate treated rats on motor activity in novel environment
Fig. 5: Effect of Methylphenidate administration on memory in Morris water maze test.
Fig. 6: Effect of challenge dose of Haloperidol in Methylphenidate treated rats on cognitive activity in Morris water maze test.
Fig. 7: Effect of Methylphenidate administration on memory in passive avoidance test.
Fig. 8: Effect of challenge dose of Haloperidol in Methylphenidate treated rats on memory in passive avoidance test
Fig. 9: Effect of Modafinil administration on motor activity in familiar environment
Fig. 10: Effect of challenge dose of Haloperidol in Modafinil treated rats on motor activity in familiar environment.
Fig. 11: Effect of Modafinil administration on motor activity in novel environment
Fig. 12: Effect of challenge dose of Haloperidol in Modafinil treated rats on motor activity in novel environment
Fig. 13: Effect of Modafinil administration on memory in Morris water maze test.
Fig. 14: Effect of challenge dose of Haloperidol in Modafinil treated rats on cognitive activity in Morris water maze test
Fig. 15: Effect of Modafinil administration on memory in passive avoidance test.
Fig. 16: Effect of challenge dose of Haloperidol in Modafinil treated rats on memory in passive avoidance test.

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Acknowledgements

This research work conducted in Neuropharmacological Research Lab, was supported and funded through mini project granted to the Department of Pharmacology, Faculty of Pharmacy, Federal Urdu University of Arts, Science and Technology, Karachi.

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  1. Department of Pharmacology, Faculty of Pharmacy, Federal Urdu University of Arts, Science and Technology , Karachi-75400, Karachi, Pakistan

    Nausheen Alam & Kulsoom Choudhary

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  1. Nausheen Alam
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Correspondence to Nausheen Alam.

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Alam, N., Choudhary, K. Haloperidol attenuates Methylphenidate and Modafinil induced behavioural sensitization and cognitive enhancement. Metab Brain Dis 33, 893–906 (2018). https://doi.org/10.1007/s11011-018-0190-x

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