HALOPERIDOL: DOPAN~iB, ACETYLCHOLINE, SEROTONTIQ, a-NORADRBNBRGIC AND NALO$ONS RECEPTORS

Since long-term neuroleptic therapy is known to alter brain dopamisergic sensitivity, we tested the effects of chronic halo-peridol administration (10 mg/kg/day for over 3 weeks) on the amount of the dopamine receptors (using 3H-apomorphine and 3H-haloperidol) is various regions of the rat brain. To test whether the changes is dopamine receptors were selectively produced, we also assayed acetylcholiae receptors (with 3H-quinuclidiayl ben-silate or 3H-QNß), alpha-noradrenergic receptors (with 3H-WB-4101), 3H-serotonia receptors and 3H~aaloaoae receptors. The specific binding of 3H-haloperidol increased significantly by 34x in the striatum and by 45x in the mesolimbic region after long-term haloperidol. The specific binding of 3H-apomorphine also increased significantly by 77Z in the striatum and 55Z in the mesolimbic area. Altpo h there was a small significant i.ricresae of 20Z in epecific~H-serotonin binding in the striatum, no such increment occurred in the hippocampus or the cerebral cortex. No significantly different binding occurred for the other 3H-ligaade in these brain regions ezcept for a 13x increase in alpha-noradrenergic binding in the cerebral cortez. These results indicate that long-term haloperidol treatment produces rather selective increases in dopamine/neuroleptic receptors, without much change in 4 other types of receptors. Such relatively selective iacreaents in these receptors may be the basis of dopaminergic superseneitivity (e.g. tardive dyekinesia) after long-term haloperidol