P2X7 purinergic receptors participate in the expression and extinction processes of contextual fear conditioning memory in mice

Author(s)

Domingos, L. B. ^[1] ; Hot, S. C. ^[1] ; Terzian, A. L. B. ^[1] ; Resstel, L. B. M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Neuropharmacology; v. 128, p. 474-481, JAN 2018.
• Web of Science Citations: 4

Abstract

The purinergic system consists of two large receptor families - P2X and P2Y. Both are activated by adenosine triphosphate (ATP), although presenting different functions. These receptors are present in several brain regions, including those involved in emotion and stress-related behaviors. Hence, they seem to participate in fear- and anxiety-related responses. However, few studies have investigated the purinergic system in threatening situations, as observed in contextual fear conditioning (CFC). Therefore, this study investigated the involvement of purinergic receptors in the expression and extinction of aversive memories. C57B1/6 background mice were submitted to the CFC protocol. Wildtype (WT) mice received i.p. injection of either a nonselective P2 receptor (P2R) antagonist, P178 (10 or 30 mg/kg); a selective P2X7 receptor (P2X7R) antagonist, A438079 (10 mg/kg); a selective P2Y1 receptor (P2Y1R) antagonist, MRS2179 (10 mg/kg); or vehicle 10 min prior to or immediately after the extinction session. Additionally, P2X7R KO mice were tested in the CFC protocol. After P2R antagonist treatment, contextual fear recall increased, while acquisition of extinction was impaired. Similar results were observed with the selective P2X7R antagonist, but not with the selective P2Y1R antagonist. Interestingly, P2X7R 1(0 mice showed increased contextual fear recall, associated with impaired acquisition of extinction, in accordance with pharmacologic P2X7R antagonism. Our results suggest that specific pharmacological or genetic blockade of P2X7R promotes anxiogenic-like effects, along with deficits in extinction learning. Thus, these receptors could present an alternative treatment of stress-related psychiatric disorders. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/08674-0 - Involvement of purinergic receptors in the expression, reconsolidation and extinction processes of contextual conditioned memory in mice
• Grantee: Luana Barreto Domingos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/22604-8 - The role or TRPV1 receptors on the modulation of aversive responses and social behavior in rodents: cellular and molecular basis of learned behavior
• Grantee: Ana Luisa Bernardes Terzian
• Support Opportunities: Scholarships in Brazil - Post-Doctoral