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甘丙肽可减弱大鼠海马中基础及抗抑郁药物诱导的细胞外5-羟色胺和去甲肾上腺素水平的升高。

Galanin attenuates basal and antidepressant drug-induced increase of extracellular serotonin and noradrenaline levels in the rat hippocampus.

作者信息

Yoshitake Takashi, Reenilä Ilkka, Ogren Sven Ove, Hökfelt Tomas, Kehr Jan

机构信息

Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.

出版信息

Neurosci Lett. 2003 Mar 27;339(3):239-42. doi: 10.1016/s0304-3940(03)00020-x.

Abstract

Galanin is co-localized with classical neurotransmitters, such as acetylcholine, serotonin (5-HT) and noradrenaline (NA) in neurons or in brain regions implicated in cognitive and affective behaviour. In the present study, the effects of galanin on extracellular 5-HT and NA levels in the rat hippocampus were measured by in vivo microdialysis under basal conditions and following systemic administration of antidepressant drugs. Galanin (1.5 nmol i.c.v.) reduced basal 5-HT and NA levels to 65% and 86% of controls, respectively. Galanin (0.5 and 1.5 nmol i.c.v.) dose-dependently attenuated the elevation of 5-HT concentrations induced by imipramine and citalopram (10 mg/kg i.p., each) from 350% to 312% and from 230% to 160%, respectively. Galanin at 1.5 nmol transiently attenuated the effect of desipramine-induced (10 mg/kg i.p.) increase in extracellular NA levels from a maximal increase of 389-296% of the predrug levels. It is concluded that intraventricularly administered galanin attenuated both basal 5-HT and NA release and antidepressant drug-induced accumulation of extracellular 5-HT and NA levels most likely via a predominant inhibitory action on serotonergic and noradrenergic neurons in the raphe and locus coeruleus, respectively. These results further emphasize a possible role of galanin in regulation of 5-HT and NA neurotransmission in depressive states and during the course of antidepressant therapy.

摘要

甘丙肽与经典神经递质,如乙酰胆碱、5-羟色胺(5-HT)和去甲肾上腺素(NA),在参与认知和情感行为的神经元或脑区中共同定位。在本研究中,通过在基础条件下以及在全身给予抗抑郁药物后进行体内微透析,测量了甘丙肽对大鼠海马细胞外5-HT和NA水平的影响。甘丙肽(1.5 nmol,脑室内注射)分别将基础5-HT和NA水平降低至对照的65%和86%。甘丙肽(0.5和1.5 nmol,脑室内注射)剂量依赖性地减弱了丙咪嗪和西酞普兰(各10 mg/kg,腹腔注射)诱导的5-HT浓度升高,分别从350%降至312%以及从230%降至160%。1.5 nmol的甘丙肽短暂减弱了地昔帕明(10 mg/kg,腹腔注射)诱导的细胞外NA水平升高的作用,该升高幅度从药物前水平的最大增加389%降至296%。得出的结论是,脑室内注射甘丙肽减弱了基础5-HT和NA的释放以及抗抑郁药物诱导的细胞外5-HT和NA水平的积累,最有可能是分别通过对中缝核和蓝斑中5-羟色胺能和去甲肾上腺素能神经元的主要抑制作用。这些结果进一步强调了甘丙肽在抑郁状态和抗抑郁治疗过程中对5-HT和NA神经传递调节中的可能作用。

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