Effects of (−)-Sulpiride on Dopamine Release in Striatum of Developing Rats: Degree of Depolarization Influences Responsiveness

The purpose of this study was to determine the effects of localized delivery of the D2 antagonist (-)-sulpiride (via microdialysis) on spontaneous and evoked dopamine release in the neostriatum of urethane-anesthetized rats 5, 10, 15, 21, and 70 days of age. Sulpiride increased spontaneous dopamine release approximately threefold relative to baseline measures, and this effect decreased with maturation. The relationship between sulpiride- and potassium-evoked release was complex; sulpiride increased evoked dopamine outflow at 5, 10, and 15 days of age. At 21 and 70 days of age, however, the effects of sulpiride were inversely related to the degree of stimulation with potassium. Furthermore, the D2 agonist quinpirole (100 microM) reversed the effects of sulpiride (10 microM), suggesting receptor mediation. These experiments demonstrate that the maturational decline in the efficacy and potency of D2 antagonism appears to be related to the degree of stimulation at the nerve terminal.