Modulation of striatal enkephalinergic neurons by antipsychotic drugs.
In this paper we review the detailed mechanisms underlying the modulation of enkephalinergic neurons by dopaminergic neurons in rat striatum. Several lines of evidence, which showed that striatal levels of [Met5]enkephalin (ME) increase after the nigrostriatal dopaminergic pathway was interrupted by hemitransection or direct administration of 6-hydroxydopamine to the substantia nigra, or after repeated injections of either reserpine or haloperidol, suggest that dopamine (DA) plays an important role in regulating the metabolism of ME-containing neurons in the striatum. The increase in ME content after repeated injections of haloperidol was found in areas heavily innervated by DA neurons such as striatum or nucleus accumbens but not in hypothalamus, brain stem, and hippocampus. Further studies suggest that striatal cholinergic interneurons may partially mediate the action of haloperidol on enkephalinergic neurons. Several studies have been carried out to determine whether the elevation of striatal ME content after haloperidol treatment was caused by an increase in the synthesis or by a decrease in the utilization of ME. The rate of decline of striatal ME content in haloperidol-treated rats was steeper than that of controls after intraventricular injection of cycloheximide, which indicated that haloperidol accelerates the turnover of ME. This hypothesis was confirmed by our recent findings that the level of mRNA coding for preproenkephalin A, determined by cell-free translation and blot hybridization with cDNA clones, is increased after repeated injections of haloperidol.
D000818:Animals; D001921:Brain / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000378:metabolism / Q000502:physiology*; D004745:Enkephalins / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007016:Hypophysectomy; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D004744:Enkephalin, Methionine; D012110:Reserpine; C033660:preproenkephalin; D006220:Haloperidol; D004298:Dopamine