Multiple 5-HT 1 autoreceptor subtypes govern serotonin release in dorsal and median raphé nuclei

Abstract

The present study investigated the possibility of multiple 5-HT 1 autoreceptor subtypes in the rostral raphé nuclei. Slices (350 μm) of rat dorsal or median raphé nucleus (DRN/MRN) were taken from male Wistar rats and superfused with artificial cerebrospinal fluid at 32°C. Fast cyclic voltammetry at carbon fibre microelectrodes was used to monitor serotonin (5-HT) release following local electrical stimulation. In both DRN and MRN, 5-HT release on short trains was reduced by the selective 5-HT 1A agonist 8-OH-DPAT (1 μM), an effect blocked by the selective 5-HT 1A antagonist WAY 100635 (0.1 μM) but not by SB 216641 (0.05 and 0.2 μM) or BRL 15572 (0.5 μM), selective antagonists at the 5-HT 1B and 5-HT 1D receptors respectively. The selective 5-HT 1B agonist CP 93129 (0.3 μM) also reduced 5-HT release in both nuclei. Its effect was blocked by SB 216641 but not by WAY 100635 or BRL 15572. The 5-HT 1D/1B agonist sumatriptan (0.5 μM) decreased 5-HT release in both DRN and MRN. In DRN, the effect of sumatriptan was blocked by BRL 15572 but not by WAY 100635 or SB 216641. In MRN, the effect of sumatriptan was not blocked by any of the above antagonists. BRL 15572 increased 5-HT release on long stimulations in DRN and MRN while WAY 100635 had no effect. SB 216641 increased 5-HT release in MRN but not DRN. WAY 100635 potentiated the effect of SB 216641 in DRN but not MRN. The data suggest that 5-HT release in DRN is controlled by 5-HT 1A, 5-HT 1B and 5-HT 1D autoreceptors. 5-HT release in MRN is controlled by 5-HT 1A and 5-HT 1B autoreceptors and another, as yet unidentified mechanism.