Mohamad Rezaei Rajab, Shiravi Abdolhossein, Seyedinia Seyed Ali, Moradi Kor Nasroallah, Vafaei Abbas Ali, Rashidy-Pour Ali
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
Student Research Committee, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Basic Clin Neurosci. 2020 Jul-Aug;11(4):507-516. doi: 10.32598/bcn.9.10.410. Epub 2020 Jul 1.
of the study: Post-training administration of glucocorticoids enhance memory consolidation of inhibitory avoidance learning. Given the involvement of 5-HT6 receptors in memory processing and the interaction of glucocorticoids with the brain serotonergic system in modulating memory processing, we investigated whether the effect of glucocorticoids on the consolidation of emotionally arousing training depends on hippocampal 5-HT6 receptors.
Rats were trained in an inhibitory avoidance task and immediately received the systemic injections of corticosterone (CORT) as well as the intra-hippocampal injections of 5-HT receptors agonist or antagonist. The memory retention test was done 48 hours after training and immediately after the behavioral test, the animals were sacrificed and the hippocampi (left and right) rapidly dissected out for molecular studies.
Post-training injections of different doses of CORT (1.25, 2.5, 5, and 10 mg/kg) enhanced memory retention in a dose-dependent manner. The CORT-induced enhancement of memory consolidation was blocked by bilateral intra-hippocampal injections of 5-HT6 receptor antagonist SB271046 (5 or 10 ng/per side), but not agonist EMD386088 (5 or 10 ng/per side). Furthermore, systemic CORT reduced 5-HT6 receptor mRNA and protein expression in the hippocampus. Both doses of 5-HT6 receptor agonist and antagonist significantly enhanced and reduced the expression of the 5-HT6 receptor, respectively, and both ligands at the higher dose (10 ng) enhanced memory consolidation. Moreover, CORT injection attenuated and enhanced, respectively, the effects of agonist and antagonist on 5-HT6 receptor expression.
These behavioral and molecular findings indicated an interaction between glucocorticoids and hippocampal 5-HT6 receptors in the consolidation of emotionally arousing experiences.
本研究中，训练后给予糖皮质激素可增强抑制性回避学习的记忆巩固。鉴于5-HT6受体参与记忆加工，且糖皮质激素与脑血清素能系统在调节记忆加工方面存在相互作用，我们研究了糖皮质激素对情绪唤起训练巩固的影响是否依赖于海马5-HT6受体。
大鼠接受抑制性回避任务训练，随后立即接受皮质酮（CORT）的全身注射以及海马内5-HT受体激动剂或拮抗剂的注射。训练48小时后进行记忆保持测试，行为测试后立即处死动物，迅速取出海马（左右两侧）用于分子研究。
训练后注射不同剂量的CORT（1.25、2.5、5和10mg/kg）以剂量依赖的方式增强了记忆保持。双侧海马内注射5-HT6受体拮抗剂SB271046（每侧5或10ng）可阻断CORT诱导的记忆巩固增强，但5-HT6受体激动剂EMD386088（每侧5或10ng）则无此作用。此外，全身注射CORT可降低海马中5-HT6受体mRNA和蛋白表达。两种剂量的5-HT6受体激动剂和拮抗剂分别显著增强和降低了5-HT6受体的表达，且两种配体在较高剂量（10ng）时均增强了记忆巩固。此外，注射CORT分别减弱和增强了激动剂和拮抗剂对5-HT6受体表达的影响。
这些行为和分子学研究结果表明，糖皮质激素与海马5-HT6受体在情绪唤起经历的巩固过程中存在相互作用。
