A microdialysis study of the in vivo release of 5-HT in the median raphe nucleus of the rat

摘要

class="enumerated" style="list-style-type:decimal">The 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.Tetrodotoxin (1 μM) and reserpine (5 mg kg⁻¹, i.p.) virtually suppressed the output of 5-HT.The 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.).The 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.The 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).These 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.