Chronic and acute adenosine A 2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB 1 receptor activation.

Autor: Mouro FM; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal., Batalha VL; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal., Ferreira DG; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal., Coelho JE; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal., Baqi Y; Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie I, University of Bonn, Germany; Department of Chemistry, Faculty of Science, Sultan Qaboos University, Muscat, Oman., Müller CE; Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie I, University of Bonn, Germany., Lopes LV; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal., Ribeiro JA; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal., Sebastião AM; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal. Electronic address: anaseb@medicina.ulisboa.pt.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2017 May 01; Vol. 117, pp. 316-327. Date of Electronic Publication: 2017 Feb 21.
DOI: 10.1016/j.neuropharm.2017.02.021
Abstrakt: Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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