Gibula-Tarlowska Ewa, Kotlinska Jolanta H
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Behav Pharmacol. 2020 Apr;31(2&3):272-282. doi: 10.1097/FBP.0000000000000557.
Acute and chronic ethanol intake, as well as ethanol withdrawal, exert learning disabilities. Of all the neurotransmitters in the brain, endogenous opioid peptides are thought to participate in ethanol effects. Kisspeptins, including kisspeptin-10, are peptides produced in the part of brain involved in the consolidation of memory and orientation. A new derivative of kisspeptin-10 is kissorphin (Tyr-Asn-Trp-Asn-Ser-Phe-NH2), a peptide with anti-opioid-activity. Hence, the aim of our study was to reveal whether kissorphin (1, 3, and 10 nmol, i.v.) was able to prevent or reverse learning deficits such as spatial memory retention and reversal learning induced by acute ethanol administration (1 × 1.75 g/kg., i.p.) and reversal learning induced by ethanol withdrawal (11-13 days from 'binge-like' ethanol input-5.0 g/kg, i.g. for 5 days) in the Barnes maze task in rats. Our study demonstrated that acute kissorphin administration prevented spatial memory (higher doses) impairments and attenuated reversal learning deficits induced by acute ethanol administration, although the reversal learning impairment may have been due to spatial learning impairments rather than cognitive flexibility impairments. Moreover, kissorphin given prior to first reversal learning trial for 3 consecutive days in the Barnes maze task during withdrawal from 'binge-like' ethanol administration, significantly attenuated cognitive flexibility impairment in the ethanol-withdrawal rats. In the acute and chronic ethanol experiments, kissorphin was the most effective at the dose of 10 nmol. In conclusion, the ethanol-induced spatial memory impairment may be reversed by pharmacological manipulation of the endogenous opioid system.
急性和慢性乙醇摄入以及乙醇戒断都会导致学习障碍。在大脑中的所有神经递质中，内源性阿片肽被认为参与了乙醇的作用。包括 kisspeptin - 10 在内的 kisspeptins 是在大脑中参与记忆巩固和定向的部分产生的肽。kisspeptin - 10 的一种新衍生物是 kissorphin（酪氨酸 - 天冬酰胺 - 色氨酸 - 天冬酰胺 - 丝氨酸 - 苯丙氨酸 - NH2），一种具有抗阿片活性的肽。因此，我们研究的目的是揭示 kissorphin（静脉注射 1、3 和 10 nmol）是否能够预防或逆转由急性乙醇给药（腹腔注射 1×1.75 g/kg）引起的空间记忆保持和逆向学习等学习缺陷，以及在大鼠 Barnes 迷宫任务中由乙醇戒断（从“暴饮样”乙醇输入 - 灌胃 5.0 g/kg，持续 5 天起 11 - 13 天）引起的逆向学习缺陷。我们的研究表明，急性给予 kissorphin 可预防空间记忆（较高剂量）损伤，并减轻急性乙醇给药引起的逆向学习缺陷，尽管逆向学习损伤可能是由于空间学习损伤而非认知灵活性损伤。此外，在从“暴饮样”乙醇给药中撤药期间，在 Barnes 迷宫任务中连续 3 天在首次逆向学习试验前给予 kissorphin，可显著减轻乙醇戒断大鼠的认知灵活性损伤。在急性和慢性乙醇实验中，kissorphin 在 10 nmol 剂量时最有效。总之，乙醇诱导的空间记忆损伤可能通过对内源性阿片系统的药理学操作来逆转。
