大麻素 CB1 和血清素能 5-HT1A 受体激动剂在小鼠背侧海马中的跨状态依赖记忆检索。
Cross state-dependent memory retrieval between cannabinoid CB1 and serotonergic 5-HT1A receptor agonists in the mouse dorsal hippocampus.
机构信息
Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
出版信息
Neurobiol Learn Mem. 2022 Jul;192:107638. doi: 10.1016/j.nlm.2022.107638. Epub 2022 May 18.
Understanding the neurobiological mechanisms of drug-related learning and memory formation may help the treatment of cognitive disorders. Dysfunction of the cannabinoid and serotonergic systems has been demonstrated in learning and memory disorders. The present paper investigates the phenomenon called state-dependent memory (SDM) induced by ACPA (a selective cannabinoid CB1 receptor agonist) and 8-OH-DPAT (a nonselective 5-HT1A receptor agonist) with special focus on the role of the 5-HT1A receptor in the effects of both ACPA and 8-OH-DPAT SDM and cross state-dependent memory retrieval between ACPA and 8-OH-DPAT in a step-down inhibitory avoidance task. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended injection sites. A single-trial step-down inhibitory avoidance task was used to assess memory retrieval and state-dependence. Post-training and/or pre-test microinjections of ACPA (1 and 2 ng/mouse) and 8-OH-DPAT (0.5 and 1 μg/mouse) dose-dependently induced amnesia. Pre-test administration of the same doses of ACPA and 8-OH-DPAT reversed the post-training ACPA- and 8-OH-DPAT-induced amnesia, respectively. This phenomenon has been named SDM. 8-OH-DPAT (1 μg/mouse) reversed the amnesia induced by ACPA (0.5, 1, and 2 ng/mouse) and induced ACPA SDM. ACPA (2 ng/mouse) reversed the amnesia induced by 8-OH-DPAT (0.25, 0.5, and 1 μg/mouse) and induced 8-OH-DPAT SDM. Pre-test administration of a 5-HT1A receptor antagonist, (S)-WAY 100,135 (0.25 and 0.5 μg/mouse), 5 min before ACPA and 8-OH-DPAT dose-dependently inhibited ACPA- and 8-OH-DPAT-induced SDM, respectively. The present study results demonstrated ACPA- and 8-OH-DPAT- induced SDM. Overall, the data revealed that dorsal hippocampal 5-HT1A receptor mechanisms play a pivotal role in modulating cross state-dependent memory retrieval between ACPA and 8-OH-DPAT.
理解与药物相关的学习和记忆形成的神经生物学机制可能有助于治疗认知障碍。在学习和记忆障碍中，已证明大麻素和 5-羟色胺能系统的功能障碍。本文研究了由 ACPA（一种选择性大麻素 CB1 受体激动剂）和 8-OH-DPAT（一种非选择性 5-HT1A 受体激动剂）诱导的状态依赖记忆（SDM）现象，特别关注 5-HT1A 受体在 ACPA 和 8-OH-DPAT SDM 效应中的作用以及 ACPA 和 8-OH-DPAT 之间的交叉状态依赖记忆检索在跳下抑制回避任务中。成年雄性 NMRI 小鼠的背侧海马 CA1 区双侧插管，所有药物均微量注射到预期的注射部位。单次试验跳下抑制回避任务用于评估记忆检索和状态依赖性。训练后和/或预测试微注射 ACPA（1 和 2 ng/只）和 8-OH-DPAT（0.5 和 1 μg/只）剂量依赖性地诱导健忘症。预测试给予相同剂量的 ACPA 和 8-OH-DPAT 分别逆转了训练后 ACPA 和 8-OH-DPAT 诱导的健忘症，分别称为 SDM。8-OH-DPAT（1 μg/只）逆转了 ACPA（0.5、1 和 2 ng/只）诱导的健忘症，并诱导了 ACPA SDM。ACPA（2 ng/只）逆转了 8-OH-DPAT（0.25、0.5 和 1 μg/只）诱导的健忘症，并诱导了 8-OH-DPAT SDM。预测试给予 5-HT1A 受体拮抗剂（S）-WAY 100,135（0.25 和 0.5 μg/只）5 分钟，可剂量依赖性地抑制 ACPA 和 8-OH-DPAT 诱导的 SDM。本研究结果表明 ACPA 和 8-OH-DPAT 诱导的 SDM。总的来说，数据显示背侧海马 5-HT1A 受体机制在调节 ACPA 和 8-OH-DPAT 之间的交叉状态依赖记忆检索中起着关键作用。
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