title: Dopamine D2 and D3 receptor preferring antagonists differentially affect striatal dopamine release and metabolism in conscious rats.
abstract: Classical neuroleptic drugs with high affinity for dopamine D2 receptors in comparison to D3 ones (haloperidol, thioproperazine and spiperone) administered i.p. acutely (0.2, 0.2 and 0.07 mg/kg, respectively) induced a pronounced increase in the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) and only a modest rise in that of dopamine in the dorsal striatum of conscious rats studied by transcerebral microdialysis. Atypical neuroleptics, clozapine and thioridazine (both 20 mg/kg), demonstrating relatively higher affinity for dopamine D3 receptor than typical ones, as well as the dopamine D3 receptor and autoreceptor preferring antagonists, cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n- propylamino)tetralin HCl ((+)-UH232) and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-propylamino)tetralin HCl ((+)-AJ76) (both 14 mg/kg), were equally effective or even more potent in increasing dopamine release than DOPAC. It is concluded that the dopamine D2/D3 receptor relative potencies of typical and atypical neuroleptics appear to correspond to their ability to affect preferentially dopamine metabolism or release in rat dorsal striatum in vivo.
authors: Laboratory of Neurochemical Pharmacology, Russian Academy of Medical Sciences, Moscow.
authors: R R
authors: RR
authors: Gainetdinov
authors: T V
authors: TV
authors: Grekhova
authors: T D
authors: TD
authors: Sotnikova
authors: K S
authors: KS
authors: Rayevsky
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine