Pitsikas Nikolaos
Department of Pharmacology, Faculty of Health Sciences, School of Medicine, University of Thessaly, Panepistimiou 3, Biopolis, 41500 Larissa, Greece.
Behav Brain Res. 2020 Sep 1;393:112778. doi: 10.1016/j.bbr.2020.112778. Epub 2020 Jun 21.
Several lines of evidence indicate that anesthetic doses of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine disrupt memory functions in rodents. The mechanism by which anesthetic ketamine produces its adverse behavioural effects is not yet clarified. The implication of nicotinic acetylcholine receptor as a potential site of action of anesthetic ketamine adverse effects on memory is proposed. We investigated the ability of α4β2 nicotinic receptor agonist ABT-418 (0.01, 0.03, 0.1 mg/kg, i.p.) and α7 nicotinic receptor agonist GTS-21 (0.3, 1, 3 mg/kg, i.p.) to counteract recognition memory deficits produced by acute post-training administration of anesthetic ketamine (100 mg/kg, i.p.) in rats. For this purpose, the novel object recognition test, a behavioural paradigm assessing recognition memory abilities in rodents was used. Post-training acute administration of GTS-21 (3 mg/kg) counteracted anesthetic ketamine-induced performance deficits in the novel object recognition memory task. By contrast, ABT-418 failed to reverse the recognition memory deficits caused by anesthetic ketamine. The present findings propose that an α7 nicotinic receptor component might modulate anesthetic ketamine's adverse effects on recognition memory.
多条证据表明，麻醉剂量的非竞争性N-甲基-D-天冬氨酸受体拮抗剂氯胺酮会破坏啮齿动物的记忆功能。麻醉性氯胺酮产生其不良行为影响的机制尚未阐明。有人提出，烟碱型乙酰胆碱受体是麻醉性氯胺酮对记忆产生不良影响的潜在作用位点。我们研究了α4β2烟碱型受体激动剂ABT-418（0.01、0.03、0.1mg/kg，腹腔注射）和α7烟碱型受体激动剂GTS-21（0.3、1、3mg/kg，腹腔注射）抵消大鼠急性训练后给予麻醉性氯胺酮（100mg/kg，腹腔注射）所产生的识别记忆缺陷的能力。为此，采用了新颖物体识别测试，这是一种评估啮齿动物识别记忆能力的行为范式。训练后急性给予GTS-21（3mg/kg）抵消了麻醉性氯胺酮诱导的新颖物体识别记忆任务中的行为缺陷。相比之下，ABT-418未能逆转麻醉性氯胺酮引起的识别记忆缺陷。目前的研究结果表明，α7烟碱型受体成分可能调节麻醉性氯胺酮对识别记忆的不良影响。
