Abstract
A kinetic analysis of central dopamine receptors in control and in experimental rats, withdrawn from long-term haloperidol treatment was made in vivo. Using the stereotyped behavior induced by apomorphine administration as the response, the relative affinity of metoclopramide as reflected by pA2 values, was examined in normal and supersensitive rats. Metoclopramide antagonized apomorphine stereotypy in a dose-dependent and competitive manner. At each dose tested, metoclopramide produced a larger rightward shift of the apomorphine dose-response curve in the control rats than in withdrawn rats. The Schild plot resulted in a straight line, the slopes being -1.2 +/- 0.3 and -0.8 +/- 0.2 for control and experimental rats, respectively. These findings suggest a decrease in receptor affinity after long-term haloperidol treatment, a concept not demonstrated in binding studies in vitro.
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