Abstract
The aim of the present study was to investigate the relationship between effects on muscle tone and D2 receptor occupancy of two typical antipsychotic drugs, raclopride and chlorpromazine, and the atypical drug, clozapine. Increased muscle tone (i.e., muscle rigidity), was measured as increases in tonic electromyographic (EMG) activity of the antagonistic muscles of the rat hind limb. D2 dopamine receptor occupancy was assessed in the striatum and substantia nigra, areas involved in the regulation of muscle tone. Raclopride and chlorpromazine produced dose-dependent increases in EMG activity associated with D2 occupancy of 68%–80% in the striatum and 67%–76% in the nigra. No significant increases in EMG were observed with clozapine which showed low D2 occupancy. The results are consistent with those from human studies showing extrapyramidal side effects were associated with striatal D2 occupancy of >70%.
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Acknowledgements
The authors thank Dr. Ian Crosbie and Ms. Juliette Neve at the Victorian College of Pharmacy, Monash University, for the generous gift of clozapine and Astra (Sweden) for raclopride. KMH is a recipient of an NH&MRC Dora Lush Biomedical Postgraduate scholarship. The financial assistance of the NHMRC and Flinders Medical Centre Foundation is gratefully acknowledged.
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Hemsley, K., Crocker, A. Raclopride and Chlorpromazine, but not Clozapine, Increase Muscle Rigidity in the Rat: Relationship with D2 Dopamine Receptor Occupancy. Neuropsychopharmacol 21, 101–109 (1999). https://doi.org/10.1016/S0893-133X(99)00010-X
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DOI: https://doi.org/10.1016/S0893-133X(99)00010-X
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