Effects of GABA, dopamine, and substance P on the release of newly synthesized 3H-5-hydroxytryptamine from rat substantia nigra in vitro

Abstract

The effects of GABA, substance P and dopamine on the release of newly synthesized ³H-5-HT were investigated, using slices of rat substantia nigra superfused with l-³H-tryptophan in vitro. GABA (50 μM) had no inhibitory effect on the potassium-evoked-release of ³H-5-HT. Substance P (50 μM) and eledoisin (50 μM) stimulated the spontaneous release of ³H-5-HT. This effect seems to be indirect and is possibly mediated by dopaminergic neurones, since the dopamine antagonist drug α-flupenthixol (1 μM) abolished the substance P-evoked release of 5-HT. Furthermore, it was found that substance P (10 μM) stimulated ³H-dopamine release from nigral slices in vitro and the dopaminergic agonist apomorphine (50 μM) also stimulated ³H-5-HT release. Substance P may, therefore, activate nigral dopaminergic neurones which then release dopamine from their dendrites. The release of dopamine may in turn stimulate 5-HT release from terminals of the raphe-nigral pathway.