DOPAMINE D-2 AND D-3 RECEPTOR PREFERRING ANTAGONISTS DIFFERENTIALLY AFFECT STRIATAL DOPAMINE RELEASE AND METABOLISM IN CONSCIOUS RATS

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, receptor than typical ones, as well as the dopamine D, receptor and autoreceptor preferring an tagonists, cis-(+)-(1S,2 R)-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 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.