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.
Akiyama
K
K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Sato
M
M
Yamada
N
N
Otsuki
S
S
D000818:Animals; D001665:Binding Sites; D002217:Carbachol / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism
D010716:Phosphatidylinositols; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D013134:Spiperone; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; C033563:haloperidol decanoate; D006220:Haloperidol; D009638:Norepinephrine