Effect of 5-hydroxy-L-tryptophan on the release of 5-HT in rat hypothalamus in vivo as measured by microdialysis.
The effect of systemic administration of the 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP) on the release of 5-HT in the lateral hypothalamus of the chloral hydrate-anaesthetized rat in vivo was examined using brain microdialysis. Administration of 5-HTP caused an immediate increase of 5-HT in dialysates, which was long lasting (greater than or equal to 140 min) and dose-dependent (30-100 mg/kg i.p.). When calcium was omitted from the perfusion medium, thereby limiting exocytosis, levels of basal 5-HT were significantly decreased and the 5-HTP-induced response of 5-HT was markedly attenuated. Administration of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (0.25 mg/kg i.p.), which selectively inhibits serotoninergic neuronal activity by activation of the somatodendritic 5-HT autoreceptor, significantly decreased basal levels of 5-HT and markedly attenuated the 5-HTP-induced increase in 5-HT. The data demonstrate that systemic administration of 5-HTP caused an increase in the release of 5-HT in the hypothalamus. Furthermore, this release occurred by a calcium-dependent mechanism (probably exocytosis), was dependent on serotoninergic neuronal activity and predominantly derived from 5-HT neurones. The findings are discussed in relation to the behavioral and neuroendocrine effects of increasing availability of the 5-HT precursor.
Gartside
S E
SE
MRC Unit of Clinical Pharmacology, University Department of Psychiatry, Littlemore Hospital, Oxford, U.K.
Cowen
P J
PJ
Sharp
T
T
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002118:Calcium / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D003956:Dialysis; D005089:Exocytosis / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D002118:Calcium