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向背海马内注射甘丙肽会损害情绪记忆,而不依赖于 5-HT 受体的激活。

Injection of galanin into the dorsal hippocampus impairs emotional memory independent of 5-HT receptor activation.

机构信息

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands; Health, Safety & Environment, VU University, Amsterdam, the Netherlands.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Atlas Antibodies, Bromma, Sweden.

出版信息

Behav Brain Res. 2021 May 7;405:113178. doi: 10.1016/j.bbr.2021.113178. Epub 2021 Feb 16.

Abstract

There is evidence that interaction between the neuropeptide galanin and the 5-HT receptor represents an integrative mechanism in the regulation of serotonergic neurotransmission. Thus, in rats intracerebroventricular (i.c.v.) galanin did not impair retention in the passive avoidance (PA) test 24 h after training, but attenuated the retention deficit caused by subcutaneous (s.c.) administration of the 5-HT receptor agonist 8-OH-DPAT. This impairment has been linked to postsynaptic 5-HT receptor activation. To confirm these results in mice, galanin was infused i.c.v. (1 nmol/mouse) in C57BL/6/Bkl mice 30 min prior to training followed by s.c. injection (0.3 mg/kg) of 8-OH-DPAT or saline 15 min before PA training. In line with previous results, i.c.v. galanin significantly attenuated the PA impairment caused by 5-HT receptor activation in mice. To study if the galanin 5-HT receptor interaction involved the dorsal hippocampus, galanin (1 nmol/mouse) was directly infused into this brain region alone or in combination with s.c. 8-OH-DPAT. However, unlike i.c.v. galanin, galanin infusion into the dorsal hippocampus alone impaired PA retention and failed to attenuate the 8-OH-DPAT-mediated PA impairment. These results indicate that the ability of i.c.v. galanin to modify 5-HT receptor activation is not directly mediated via receptor interactions in the dorsal hippocampus. Instead, the galanin-mediated PA impairment suggests an important inhibitory role of galanin receptors in the dorsal hippocampus for acquisition (encoding) and/or consolidation of emotional memory. In addition, the interaction between galanin and 5-HT receptors probably involves a wide serotonergic network that is important for the integration of emotional and cognitive behaviors.

摘要

有证据表明,神经肽甘丙肽与 5-HT 受体之间的相互作用代表了调节 5-羟色胺能神经传递的一种整合机制。因此,在大鼠中,脑室内(i.c.v.)给予甘丙肽不会损害训练后 24 小时的被动回避(PA)测试中的保留,而是减弱了皮下(s.c.)给予 5-HT 受体激动剂 8-OH-DPAT 引起的保留缺陷。这种损伤与突触后 5-HT 受体的激活有关。为了在小鼠中证实这些结果,在 C57BL/6/Bkl 小鼠接受训练前 30 分钟,将甘丙肽(1 nmol/只)脑室内输注(i.c.v.),然后在 PA 训练前 15 分钟皮下(s.c.)注射 8-OH-DPAT 或生理盐水(0.3 mg/kg)。与之前的结果一致,脑室内给予甘丙肽显著减弱了 5-HT 受体激活引起的 PA 损伤。为了研究甘丙肽与 5-HT 受体的相互作用是否涉及背侧海马,甘丙肽(1 nmol/只)单独或与皮下注射 8-OH-DPAT 一起直接输注到该脑区。然而,与脑室内给予甘丙肽不同,单独向背侧海马输注甘丙肽会损害 PA 的保留,并且不能减弱 8-OH-DPAT 介导的 PA 损伤。这些结果表明,脑室内甘丙肽修饰 5-HT 受体激活的能力不是通过背侧海马中的受体相互作用直接介导的。相反,甘丙肽介导的 PA 损伤表明甘丙肽受体在背侧海马中对获取(编码)和/或情绪记忆的巩固具有重要的抑制作用。此外,甘丙肽与 5-HT 受体之间的相互作用可能涉及一个广泛的 5-羟色胺能网络,该网络对情绪和认知行为的整合很重要。

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