Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden.
Synapse. 2014 May;68(5):179-93. doi: 10.1002/syn.21730. Epub 2014 Feb 3.
The neuropeptide galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. galanin correlated well with the density of 5-HT and galanin nerve terminals and galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of galanin-positive terminals and low/moderate galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of galanin infusions on 5-HT release and distribution of galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release.
神经肽甘丙肽参与调节情感行为,包括调节 5-HT 信号。在这里,我们通过在自由活动的大鼠中使用微透析,研究了脑内(i.c.)和脑室内(i.c.v.)注射甘丙肽对内侧前额叶皮层(mPFC)、腹侧海马 CA1 区(vHPC)、中央杏仁核(CeA)、下丘脑腹内侧核腹外侧部(VMHvl)和尾状核腹侧部(CPu)中细胞外 5-HT 水平的基础的影响。这些结果与甘丙肽、5-HT 和去甲肾上腺素(NA)神经末梢的分布的平行免疫组织化学分析进行了比较,并与甘丙肽受体的数据进行了比较。甘丙肽脑室内给药显著降低 mPFC 中的 5-HT 水平至 79%,降低 vHPC 中的 5-HT 水平至 72%。局部给予甘丙肽导致 vHPC 中的 5-HT 水平持续下降至 88%,CeA 中的 5-HT 水平中度下降,而 mPFC 中的 5-HT 水平显著增加至 121%。i.c.甘丙肽的这些作用与 mPFC、vHPC 和 CeA 中 5-HT 和甘丙肽神经末梢和甘丙肽受体放射自显影的密度密切相关。i.c.或 i.c.v.甘丙肽对 CPu 或 VMHvl 中的 5-HT 水平没有影响,这与甘丙肽阳性末梢数量较少和甘丙肽受体密度较低/中等相一致。甘丙肽经常与 NA 共存,但从未在 5-HT 末梢中检测到。总之,这些结果表明,甘丙肽输注对 5-HT 释放的影响与甘丙肽及其受体的分布之间存在神经解剖学相关性,并且脑室内和脑内给药可以对 5-HT 释放产生相反的影响。