PARTIAL AND FULL DOPAMINE D-1 AGONISTS PRODUCE COMPARABLE INCREASES IN VENTRAL PALLIDAL NEURONAL-ACTIVITY - CONTRIBUTION OF ENDOGENOUS DOPAMINE

Systemic administration of the partial DA D-1 agonist SKF38393 often i ncreases the firing rate of neurons in the VP of rats. This study exte nded this finding by comparing responses to (+/-)SKF38393 with those p roduced by two D-1 agonists that have greater intrinsic efficacy, (+/- )SKF82958 and (+/-)DHX. The role of endogenous DA in D-1 agonist-induc ed effects also was examined. Extracellular recordings of single VP ne urons were obtained in chloral hydrate-anesthetized male rats, to whic h equimolar doses of SKF38393, SKF82958 or DHX were administered i.v. Each of the agonists increased firing rate in about 45% of the neurons tested. Moreover, each agonist produced the same maximal increase in activity (161% to 178% of spontaneous rate). Acute decreases in synapt ic DA, produced by either GEL or combined treatment with reserpine and AMPT, potentiated the maximal increase in activity evoked by SKF38393 or SKF82958. These DA-depleting treatments did not alter the percenta ge of neurons that displayed this response to D-1 agonist challenge. L ow doses of the selective D-1 antagonists SCH23390 or SCH39166 general ly attenuated the agonist-induced changes in firing rate, supporting t he conclusion that D-1 receptors were activated by SKF38393, SKF82958 and DHX. Thus, these three D-1 agonists, which produce different maxim al increases in striatal adenylyl cyclase activity, had comparable eff icacy to increase VP neuronal activity. A reduction in endogenous DA e nhanced the D-1 agonist-induced effects, possibly through a reduction in inhibitory influences on VP neurons that are mediated by other DA r eceptor subtypes.