Gartside S E, Cowen P J, Sharp T
MRC Unit of Clinical Pharmacology, University Department of Psychiatry, Littlemore Hospital, Oxford, U.K.
Neuropharmacology. 1992 Jan;31(1):9-14. doi: 10.1016/0028-3908(92)90154-h.
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.
采用脑微透析技术，研究了水合氯醛麻醉大鼠体内系统给予5-羟色胺（5-HT）前体5-羟-L-色氨酸（5-HTP）对下丘脑外侧5-HT释放的影响。给予5-HTP后，透析液中5-HT立即增加，这种增加持续时间长（大于或等于140分钟）且呈剂量依赖性（腹腔注射30-100毫克/千克）。当灌注介质中不含钙，从而限制胞吐作用时，基础5-HT水平显著降低，5-HTP诱导的5-HT反应明显减弱。给予5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（腹腔注射0.25毫克/千克），通过激活树突体5-HT自身受体选择性抑制5-羟色胺能神经元活性，显著降低基础5-HT水平，并明显减弱5-HTP诱导的5-HT增加。数据表明，系统给予5-HTP导致下丘脑5-HT释放增加。此外，这种释放通过钙依赖机制（可能是胞吐作用）发生，依赖于5-羟色胺能神经元活性，且主要来源于5-HT神经元。结合增加5-HT前体可用性的行为和神经内分泌效应，对这些发现进行了讨论。
