Campos R C, Parfitt G M, Polese C E, Coutinho-Silva R, Morrone F B, Barros D M
Programa de Pós-graduação em Ciências Fisiológicas - Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Laboratório de Neurociências, Universidade Federal do Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil.
Instituto de Ciências Biológicas, Laboratório de Neurociências, Universidade Federal do Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil.
Neuroscience. 2014 Nov 7;280:220-30. doi: 10.1016/j.neuroscience.2014.09.017. Epub 2014 Sep 18.
Adenosine triphosphate (ATP) plays a role in cell signaling. It was soon proposed that ATP activates ionotropic P2X receptors, exerting an influence on neurons as well as on glial cells. In addition to the fact that the activation of P2X and P2Y receptors can stimulate or inhibit the release of glutamate from rat hippocampal neurons, the release of ATP has been implicated in hippocampal long-term potentiation (LTP). Through different behavioral paradigms, this study aimed to investigate the participation of P2X7R in genetically modified (knockout (KO)) mice with the suppressed expression of this receptor and in the pharmacological blockage of this receptor in rats, as well as to evaluate the effect of environmental enrichment on potential mnemonic deficits. The results suggest that P2X7R participates in aversive memory processes: pharmacological blockage with the selective P2X7R antagonist, A-740003, in different time frames elicited dose-dependent impairments in memory acquisition, consolidation and retrieval in rats that were submitted to the contextual fear-conditioning (FC) task, and the deletion of P2X7R hampered the aversive memory processes of mice that were subjected to the FC paradigm. Experiments using mice that were subjected to environmental enrichment suggest that this form of stimulation reverses mnemonic impairments that are ascribed to the absence of the P2X7R, suggesting that these receptors do not participate on such a reversal. Finally, no alterations were observed in the habituation memory of P2X7KO mice.
三磷酸腺苷（ATP）在细胞信号传导中发挥作用。很快有人提出，ATP可激活离子型P2X受体，对神经元和神经胶质细胞均产生影响。除了P2X和P2Y受体的激活可刺激或抑制大鼠海马神经元谷氨酸释放这一事实外，ATP的释放还与海马长时程增强（LTP）有关。通过不同的行为范式，本研究旨在调查P2X7R在该受体表达受抑制的基因改造（敲除（KO））小鼠以及大鼠中该受体的药理学阻断中的参与情况，并评估环境富集对潜在记忆缺陷的影响。结果表明，P2X7R参与厌恶记忆过程：在不同时间框架内用选择性P2X7R拮抗剂A-740003进行药理学阻断，会导致接受情境恐惧条件反射（FC）任务的大鼠在记忆获取、巩固和检索方面出现剂量依赖性损伤，而P2X7R的缺失阻碍了接受FC范式的小鼠的厌恶记忆过程。使用接受环境富集的小鼠进行的实验表明，这种刺激形式可逆转归因于P2X7R缺失的记忆损伤，这表明这些受体不参与这种逆转。最后，未观察到P2X7KO小鼠的习惯化记忆有改变。
