|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|131038||2018||25 صفحه PDF||سفارش دهید||6606 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Neuropharmacology, Volume 128, January 2018, Pages 474-481
The purinergic system consists of two large receptor families â 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. C57Bl/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 30Â mg/kg); a selective P2X7 receptor (P2X7R) antagonist, A438079 (10Â mg/kg); a selective P2Y1 receptor (P2Y1R) antagonist, MRS2179 (10Â mg/kg); or vehicle 10Â 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 KO 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.