title: Pharmacological blockage and P2X7 deletion hinder aversive memories: reversion in an enriched environment.
abstract: 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.
authors.affiliation: 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.
authors.forename: R C
authors.initials: RC
authors.lastname: Campos
authors.affiliation: 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.
authors.forename: G M
authors.initials: GM
authors.lastname: Parfitt
authors.affiliation: Instituto de Ciências Biológicas, Laboratório de Neurociências, Universidade Federal do Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil.
authors.forename: C E
authors.initials: CE
authors.lastname: Polese
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Coutinho-Silva
authors.affiliation: Instituto de Toxicologia e Farmacologia, Pontifícia Universidade Católica de Porto Alegre (PUC-RS), Brazil.
authors.forename: F B
authors.initials: FB
authors.lastname: Morrone
authors.affiliation: 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. Electronic address: barrosdm@yahoo.com.br.
authors.forename: D M
authors.initials: DM
authors.lastname: Barros
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004777:Environment; D005239:Fear / Q000187:drug effects / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology; D006799:Housing, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000502:physiology*
chemical_list: C515928:(N-(1-(((cyanoimino)(5-quinolinylamino) methyl) amino)-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide); D000081:Acetamides; C546469:P2rx7 protein, mouse; C546470:P2rx7 protein, rat; D058920:Purinergic P2X Receptor Antagonists; D011804:Quinolines; D058486:Receptors, Purinergic P2X7
keywords: P2X7; aversive memory; fear conditioning; purinergic system; spatial memory