- 1The present study has examined several characteristics of the release of 5-HT in the median raphe nucleus in terms of its dependence of nerve impulse, provenance of a vesicular storage fraction as well as the regulatory role played by 5-HT1A receptors.
- 2Tetrodotoxin (1 μm) and reserpine (5 mg kg−1, i.p.) virtually suppressed the output of 5-HT.
- 3The administration of EEDQ (10 mg kg−1, i.p.) did not alter the basal release of 5-HT but abolished the reduction of 5-HT release induced by 8-OH-DPAT (0.1 mg kg−1, s.c.).
- 4The perfusion of 1–100 μm of 8-OH-DPAT or the novel 5-HT1A agonist BAY×3702 decreased the efflux of 5-HT, whereas the perfusion of the 5-HT1A antagonist WAY-100635 failed to alter 5-HT release.
- 5The decrease in dialysate 5-HT induced by 100 μm 8-OH-DPAT was reversed by the concurrent perfusion of 100 μm WAY-100635. Also, the perfusion of 100 μm WAY-100635 for 2 h inhibited partly the reduction of 5-HT release evoked by the systemic administration of 8-OH-DPAT (0.1 mg kg−1).
- 6These results indicate that extracellular 5-HT in the median raphe nucleus is stored in vesicles and released in an impulse-dependent manner. Also, the basal release of 5-HT in the median raphe nucleus does not appear to be under the tonic control of somatodendritic 5-HT1A receptors by endogenous 5-HT. Instead, this feedback mechanism seems to be triggered when an excess of the transmitter or a 5-HT1A agonist is present in the extracellular space of the median raphe nucleus.
British Journal of Pharmacology (1998) 125, 1361–1367; doi:10.1038/sj.bjp.0702206