Raclopride and chlorpromazine, but not clozapine, increase muscle rigidity in the rat: Relationship with D₂ dopamine receptor occupancy

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%. Copyright (C) 1999 American College of Neuropsychopharmacology.