The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232; a microdialysis study.
The in vivo neurochemical profiles of haloperidol, raclopride and the dopamine D3 and autoreceptor preferring dopamine receptor antagonists (+)-UH232 and (+)-AJ76 on dopamine release and metabolism in the dorsal striatum and in the nucleus accumbens are described. It is shown that both (+)-UH232 and especially (+)-AJ76 have different effects on brain dialysate dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) as compared to haloperidol or raclopride. It is suggested that the relative increase in dialysate dopamine over the relative increase in DOPAC is a neurochemical fingerprint, unique for different dopamine receptor antagonists. As a consequence the increased release and metabolism of dopamine after systemic administration of dopamine receptor antagonists may be controlled by different receptors and different dopamine antagonists can partly distinguish between these receptors. This may be due to their different interactions with different dopamine D2 type receptors. It is finally concluded that (+)-UH232 and especially (+)-AJ76 seem to prefer release regulating autoreceptors at the level of the axon terminals.
Waters
N
N
Department of Pharmacology, University of Göteborg, Sweden.
Lagerkvist
S
S
Löfberg
L
L
Piercey
M
M
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; D017660:Autoreceptors / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects
D017660:Autoreceptors; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; 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; D006220:Haloperidol; D004298:Dopamine