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Chronic administration of the neuroleptic haloperidol, the calcium channel antagonist nitrendipine, and the calcium channel antagonist neuroleptic pimozide produce differential effects on rat striatal 3H-spiperone binding. Following 7 days of 10 mg/kg i.p. administration, haloperidol significantly increases (p< 0.01) dopamine D2 receptor binding to 123% ± 6% of control values, whereas pimozide treatment significantly reduces (p < 0.001) striatal 3H-spiperone binding to 46% ± 6% of control values. Chronic administration of the calcium channel antagonist nitrendipine does not alter 3H -spiperone binding relative to control values. Saturation analysis reveals an increase in Bmaxfollowing chronic haloperidol and a decrease in Bmaxfollowing chronic pimozide treatment. No alterations in muscarinic cholinergic sites, dopamine uptake sites, or calcium channel antagonist sites result following chronic drug administration. These results are the first demonstration of a decrease in dopamine D2 binding sites after chronic neuroleptic treatment.
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Received in revised form: April 4, 1986
Received: December 23, 1985We would like to thank Faith Smith for assistance in preparation of the manuscript and David Liu for preparation of the artwork.
☆Supported in part by the Pimley Research Fund at Stanford University, the John A. and George L. Hartford Foundation, and the Alfred P. Sloan Foundation. L.H.T. was supported by NIMH Research Service Award F32 MH09099-01.
© 1986 Published by Elsevier Inc.