Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction

• Published in: Neuroscience Vol. 154; no. 4; pp. 1648 - 1655
• Main Authors: de Oliveira Alvares, L, Pasqualini Genro, B, Diehl, F, Molina, V.A, Quillfeldt, J.A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 17.07.2008; Elsevier
• Subjects: AM251; anandamide; Animals; Arachidonic Acids - pharmacology; Biological and medical sciences; Cannabinoid Receptor Modulators - pharmacology; CB1 receptors; Conditioning, Operant; dorsal hippocampus; Endocannabinoids; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - physiology; Male; Memory - drug effects; Memory - physiology; memory extinction; memory reconsolidation; Neurology; Piperidines - pharmacology; Polyunsaturated Alkamides - pharmacology; Pyrazoles - pharmacology; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - metabolism; Vertebrates: nervous system and sense organs; FAAH; fatty-acid amide hydrolase; 5,6-dichloro-1-b- d-ribofuranosylbenzimidazole; memory extinction; CS; dorsal hippocampus; conditioned stimulus; unconditioned stimulus; AM251; DCS; DRB; CB1 receptors; N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; d-cycloserine; anandamide; AEA; memory reconsolidation; US; CB1 cannabinoid receptor; Memory; Central nervous system; Hippocampus; Encephalon; Anandamide
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.05.005

Abstract Retrieval of a consolidated memory triggers a number of processes which depend, among other factors, on the duration of the reactivation session: reconsolidation requires a brief reactivation session, and extinction, a prolonged one. The scope of this study is to explore the potential role of the hippocampal endocannabinoid system on reconsolidation and extinction processes. Bilateral infusion of the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) into the CA1 region of the dorsal hippocampus of Wistar rats after memory reactivation facilitated the reconsolidation of the contextual fear conditioning memory. The inhibition of protein synthesis with DRB in the same brain region blocked memory reconsolidation. Both effects were persistent, lasting up to 7 days after the first retrieval experience. In contrast, the local infusion of anandamide blocked memory reconsolidation, an effect that was antagonized by the combined administration of anandamide with a subthreshold dose of a CB1 antagonist, supporting a CB1-mediated role of the hippocampal endocannabinoid system in the modulation of the memory reconsolidation. Local infusion of AM251 into CA1 blocked memory extinction whereas the administration of anandamide facilitated it; however, when combined with a subthreshold concentration of the CB1 antagonist, anandamide did not affect the extinction process. The clear-cut, opposite effects observed in each situation suggest a possible role of the hippocampal endocannabinoid system as a switching mechanism deciding which processes will take place, either maintaining the original memory (reconsolidation) or promoting a new learning (extinction).