Opposing role of dopamine D1 and D2 receptors in modulation of rat nucleus accumbens noradrenaline release

The role of dopamine receptors in the modulation of nucleus accumbens noradrenaline release was investigated in superfused rat brain slices. At concentrations of ≤1 μM, dopamine enhanced, whereas at higher concentrations dopamine inhibited electrically evoked [³H]noradrenaline release. The D1 receptor agonist SKF-38393 increased, whereas the D2 agonist quinpirole inhibited evoked [³H]noradrenaline release. These effects were attenuated by the D1 antagonist SCH-23390 and the D2 antagonist (-)- sulpiride, respectively, indicating that accumbens noradrenaline release is regulated by stimulatory D1 and inhibitory D2 receptors. Whereas (-)- sulpiride enhanced, SCH-23390 did not reduce evoked accumbens [³H]noradrenaline release, indicating a tonic activation of D2 receptors only. Given the similar apparent affinity of dopamine for D1 and D2 receptors in striatal slices, the lack of tonic D1 receptor activation suggests that D1, unlike D2, receptors are extrasynaptically localized. No dopaminergic modulation of noradrenaline release was observed in rat medial prefrontal cortex or amygdala slices. To examine the regulation of accumbens noradrenaline release under conditions of increased dopaminergic activity, measurements were made using slices of amphetamine-pretreated rats. In these slices, the electrically evoked release of [³H]dopamine and [³H]noradrenaline was enhanced. The increasing effect of (-)-sulpiride on noradrenaline release was augmented, and SCH-23390 almost completely reversed this enhancement of [³H]noradrenaline release. These data suggest that whereas although under a moderate dopaminergic tone, accumbens noradrenaline release is mainly regulated by inhibitory D2 receptors, under circumstances of increased dopaminergic activity, recruitment of extrasynaptic stimulatory D1 receptors contributes to enhancement of noradrenaline release.