Influence of lithium on biochemical manifestations of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment.
The effects of prolonged treatment with dietary lithium and/or haloperidol (infused by means of osmotic minipumps) on biochemical parameters indicative of striatal dopamine target cell supersensitivity have been investigated in the rat. When given concomitantly with haloperidol, lithium failed to prevent the fall of striatal dopamine metabolites observed 2 days following withdrawal and the tolerance to the elevation of dopamine metabolites in response to challenge with the neuroleptic during withdrawal. Prolonged treatment with lithium also failed to modify the changes in nigral dihydroxyphenylacetic acid levels and in striatal acetylcholine levels which occur under chronic neuroleptic treatment. Chronic dietary lithium alone consistently elevated substance P levels in substantia nigra. The usual decrease in nigral levels of the peptide that occurs in response to chronic treatment with haloperidol was prevented in animals treated concomitantly with lithium. These data suggest that the mechanism whereby lithium stabilizes dopaminergic supersensitivity does not seem to involve an action of the compound on the neuronal mechanisms regulating the activity of the nigro-striatal dopaminergic system or on striatal cholinergic neurons but may be related to the restoration of normal striato-nigral substance P ergic transmission.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013378:Substantia Nigra / Q000378:metabolism
D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D008094:Lithium; D006220:Haloperidol; D000109:Acetylcholine; D004298:Dopamine; D006719:Homovanillic Acid