Yoshitake Takashi, Reenilä Ilkka, Ogren Sven Ove, Hökfelt Tomas, Kehr Jan
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
Neurosci Lett. 2003 Mar 27;339(3):239-42. doi: 10.1016/s0304-3940(03)00020-x.
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.
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。