Tolerance in the motor effects of haloperidol: Association with the enhanced serotonin-2C receptor dependant responses. | [Pakistan Journal of Biochemistry and Molecular Biology • 2008]

Author(s):

1. Huma Ikram: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi, Pakistan

2. Noreen Samad: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi, Pakistan

3. Darakhshan J. Haleem: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi, Pakistan

Abstract:

An important goal of current neuroleptic research is to evaluate the role of serotonin (5-HT; Hydroxytryptamine) in the elicitation of extrapyramidal symptoms (EPS) following long term administration of neuroleptic compounds. Present study is designed to monitor the effectiveness of 5-HT2C receptors in rats exhibiting tardive vacuous chewing movements (tVCMs) following long term administration of haloperidol. Haloperidol injected at a dose of lmg/kg impaired motor coordination but tolerance developed after 3 week of repeated haloperidol administration. Two days after withdrawal from repeated (5 weeks) administration of haloperidol, the animals were injected with vehicle (saline; 1mg/kg of body weight) or challenge drug (m-CPP; 3mg/ml/kg). Motor coordination on rotorod was monitored 30min post injection. Animals were decapitated (4hr post injection) to collect dorsal striatum samples for neurochemical analysis by HPLC-EC method. Results showed that m-CPP induced impairment of motorcoordination was greater in rats repeatedly injected with haloperidol. m-CPP induced decreases of dopamine metabolism were also greater in repeated haloperidol- than repeated saline injected animals. Results suggest that an increase in the effectiveness of 5-HT2C receptors is produced following long term administration of haloperidol. Role of responsiveness of 5-HT2C receptors in the elicitation of EPS is discussed.

Page(s): 119-124

DOI: DOI not available

Published: Journal: Pakistan Journal of Biochemistry and Molecular Biology , Volume: 41, Issue: 3, Year: 2008

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