3H-Spiroperidol association and dissociation rate constants were determined in rat striatal homogenates in the presence of known concentrations of unlabelled haloperidol. The rate of 3H-spiroperidol association was progressively decreased in the presence of increasing concentrations of haloperidol and no changes were seen in 3H-spiroperidol dissociation rate constants. Measuring changes in 3H-spiroperidol association rate constants permitted detection of 0.1 pmol/ml unlabelled haloperidol in assay homogenates. Then, male Sprague-Dawley rats received daily injections of haloperidol (1.5 mg/kg) for 1-21 days. Twenty-four hours after the last injection, 3H-spiroperidol kinetic rate constants and Kd values were measured and found to be unchanged in all treatment groups. These findings suggest that, under these conditions of drug withdrawal and tissue preparation, which are widely employed in studies of chronic neuroleptic administration, residual haloperidol does not interfere with the estimation of 3H-spiroperidol binding parameters.
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