Comparison between radiolabelled and endogenous dopamine release from rat striatal slices: effects of electrical field stimulation and regulation by D2-autoreceptors

Abstract

Direct comparisons have been made between the release of radiolabelled and endogenous dopamine from superfused rat striatal slices prelabelled with ³H-dopamine. Both spontaneous release and release evoked by electrical field stimulation (3 Hz, 2 min) were measured using a high-sensitivity HPLC system with electrochemical (coulometric) detection, plus scintillation counting of chromatographically separated superfusate fractions. Two periods of electrical stimulation released similar amounts of endogenous dopamine, but the second stimulation released much less ³H-dopamine than did the first, although the levels of spontaneous release immediately before the two stimuli were similar. Substantial increases in endogenous 3,4-dihydroxy phenyl acetic acid (DOPAC) release but only minor increases in ³H-DOPAC release occurred following the two stimuli. The dopamine agonist pergolide (1 μM) reduced the electrically-stimulated release of both ³H-dopamine and endogenous dopamine to a similar extent, whilst the D₂-selective antagonist sulpiride (1 μM) produced large increases in both ³H-dopamine and endogenous dopamine electrically-stimulated release. In addition, spontaneous release of both ³H-dopamine and endogenous dopamine were decreased by pergolide and increased by sulpiride. Co-addition of sulpiride and pergolide produced lesser increases than those seen with sulpiride alone. These studies indicate that, despite major differences between ³H-dopamine and endogenous dopamine release in response to various stimuli, their regulation by D₂-autoreceptors appears similar; a novel finding being the modulation of spontaneous ³H-dopamine release by autoreceptors. This suggests that these autoreceptors do not selectively affect any specific intracellular pool contributing to dopamine release under these conditions, though it should be noted that the prelabelling process itself may alter the intracellular sources of subsequent release.