Intracerebral infusion of (+)-AJ76 and (+)-UH232: effects on dopamine release and metabolism in vivo.
The dopamine D3- and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232 were administered locally in the striatum and the nucleus accumbens. Their effects on dialysate dopamine and 3,4-di-hydroxyphenylacetic acid (DOPAC) were measured and compared with the effects of raclopride. (+)-AJ76 and (+)-UH232 but not raclopride seem to interact primarily with dopamine receptors in the terminal regions of the A9 and A10 dopaminergic fibers to exert their maximal effect on dopamine release in vivo. Thus, (+)-AJ76 and (+)-UH232 seem to recruit different dopamine receptor populations as compared to raclopride. Though the dopamine receptor antagonist-induced effects on dopamine release seem to be mediated mainly by dopamine receptors in the terminal areas, the effects on DOPAC by the different antagonists seem to be mediated mainly via effects elsewhere, presumably at the somatodendritic autoreceptors. Thus, it is suggested that the regulation of extracellular dopamine and DOPAC after treatment with dopamine receptor antagonists are subjected to different control mechanisms.
Waters
N
N
Department of Pharmacology, University of Göteborg, Sweden.
Hansson
L
L
Löfberg
L
L
Carlsson
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D004333:Drug Administration Routes; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018492:Dopamine Antagonists; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D020891:Raclopride; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; C045971:UH 232; D004298:Dopamine; D006719:Homovanillic Acid