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

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 rat striatum 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.