Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation. (1st May 2017)

• Record Type: Journal Article
• Authors: Mouro, Francisco M.; Batalha, Vânia L.; Ferreira, Diana G.; Coelho, Joana E.; Baqi, Younis; Müller, Christa E.; Lopes, Luísa V.; Ribeiro, Joaquim A.; Sebastião, Ana M.
• Is Part Of: Neuropharmacology. Volume 117(2017)
• Page Start: 316
• Page End: 327
• Publication Date: 2017-05-01
• Subjects: Caffeine -- Cannabinoid receptor 1 -- Adenosine A2A receptor -- Istradefylline -- Novel object recognition -- Memory; AM251 N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide -- A1R adenosine A1 receptor -- A2AR adenosine A2A receptor -- C57BL6/J Black-Six mice -- CBR cannabinoid receptor -- CB1R cannabinoid receptor 1 -- CB2R cannabinoid receptor 2 -- CZ Open Field Test Central zone -- DMSO Dimethylsulfoxide -- EPM Elevated Plus Maze Test -- GABA Gamma-Aminobutyric acid(γ-Aminobutyric acid) -- I.P intraperitoneal injection -- IZ Open-Field Test Intermediary zone -- KW-6002 istradefylline -- NOR Novel Object Recognition Test -- PZ Open-field Test Peripheral zone -- SCH 58261 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4, 3-e]-1, 2, 4-triazolo[1, 5 c]pyrimidine) -- VGCCs Voltage-gated calcium channels -- WIN55, 212-2 (R)-(+)-[2, 3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1, 2, 3-de]-1, 4-benzoxazin-6-yl]-1-naphthyl-methanone mesylate; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.02.021
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB1 receptor (CB1 R)-induced memory deficits through an adenosine A1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A2A receptors (A2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB1 /CB2 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 A2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A2A 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 CB1 Rs was assessed by using the CB1 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 CB1 R-mediated memory disruption is prevented by antagonism of adenosine A2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB1 R drugs is desired. Highlights: Acute cannabinoid CB1 receptor activation disrupts long-term memory. Adenosine A2A receptor blockade prevents CB1 receptor-mediated disruptive effects. Both acute and chronic blockade of adenosine A2A receptors is effective. A2A receptor blockade must occur during information coding/consolidation. A2A receptor blockade only during retrieval is ineffective.