Effect of Chronic Administration of Haloperidol (Intermittently) and Haloperidol‐Decanoate (Continuously) on D₂ Dopamine and Muscarinic Cholinergic Receptors and on Carbachol‐Stimulated Phosphoinositide Hydrolysis in the Rat Striatum

Abstract: It has been reported that apomorphine‐induced stereotypy is sensitized after a chronic intermittent administration of haloperidol (HPD), but not after a chronic continuous exposure to haloperidol‐decanoate (HPD‐D). The present study was undertaken to investigate changes in the D₂ dopamine and muscarinic receptors in the ratstriatum after the administration of HPD intermittently and HPD‐D continuously. The number of striatal [³H] spiperone binding sites increased significantly after HPD‐D, but did not change after HPD. Neither the number of [³H](–)QNB binding sites nor carbachol‐stimulated phosphoinositide hydrolysis changed after either HPD or HPD‐D. These results indicate that the increase in striatal D₂ receptors in rats administered HPD‐D represents behavioral and biochemical tolerance, and that neither the D₂ dopamine receptor supersensitivity nor muscarinic receptor hyposensitivity underlies sensitization of apomorphine‐induced stereotypy.