Dopamine D 2 and D 3 receptor preferring antagonists differentially affect striatal dopamine release and metabolism in conscious rats

Abstract

Classical neuroleptic drugs with high affinity for dopamine D 2 receptors in comparison to D 3 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 D 3 receptor than typical ones, as well as the dopamine D 3 receptor and autoreceptor preferring antagonists, cis(+)-(1 S,2 R)-5-methoxy-1-methyl-2-(di- n-propylamino)tetralin HCl ((+)-UH232) and cis-(+)-(1 S,2 R)-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 D 2/D 3 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.