A microdialysis study of the in vivo release of 5-HT in the median raphe nucleus of the rat.
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 microM) 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 microM of 8-OH-DPAT or the novel 5-HT1A agonist BAY x 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 microM 8-OH-DPAT was reversed by the concurrent perfusion of 100 microM WAY-100635. Also, the perfusion of 100 microM 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.
Adell
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Department of Neurochemistry, IIBB, CSIC, Barcelona, Spain.
Artigas
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D001578:Benzopyrans; D010879:Piperazines; D011725:Pyridines; D011804:Quinolines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; C111221:repinotan hydrochloride; D012701:Serotonin; D013779:Tetrodotoxin; C000470:EEDQ; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine