The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction

Ricardo Marcelo Sachser; Ana Paula Crestani; Jorge Alberto Quillfeldt; Tadeu Mello E Souza; Lucas de Oliveira Alvares

doi:10.1101/lm.039891.115

The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction

Learn Mem. 2015 Nov 16;22(12):584-8. doi: 10.1101/lm.039891.115. Print 2015 Dec.

Authors

Ricardo Marcelo Sachser¹, Ana Paula Crestani², Jorge Alberto Quillfeldt², Tadeu Mello E Souza³, Lucas de Oliveira Alvares⁴

Affiliations

¹ Laboratório de Neurobiologia da Memória Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 90046-900, Brazil.
² Laboratório de Psicobiologia e Neurocomputação, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 90046-900, Brazil.
³ Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90046-900, Brazil Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 90046-900, Brazil.
⁴ Laboratório de Neurobiologia da Memória Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 90046-900, Brazil lucas.alvares@ufrgs.br.

Abstract

Despite the fact that the cannabinoid receptor type 1 (CB1R) plays a pivotal role in emotional memory processing in different regions of the brain, its function in the retrosplenial cortex (RSC) remains unknown. Here, using contextual fear conditioning in rats, we showed that a post-training intra-RSC infusion of the CB1R antagonist AM251 impaired, and the agonist CP55940 improved, long-term memory consolidation. Additionally, a post-reactivation infusion of AM251 enhanced memory reconsolidation, while CP55940 had the opposite effect. Finally, AM251 blocked extinction, whereas CP55940 facilitated it and maintained memory extinguished over time. Altogether, our data strongly suggest that the cannabinoid system of the RSC modulates emotional memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cannabinoid Receptor Agonists / pharmacology
Cannabinoid Receptor Antagonists / pharmacology
Catheters, Indwelling
Cerebral Cortex / drug effects
Cerebral Cortex / metabolism*
Conditioning, Psychological / drug effects
Conditioning, Psychological / physiology
Cyclohexanols / pharmacology
Extinction, Psychological / drug effects
Extinction, Psychological / physiology*
Fear / drug effects
Fear / physiology*
Male
Memory Consolidation / drug effects
Memory Consolidation / physiology*
Piperidines / pharmacology
Pyrazoles / pharmacology
Rats, Wistar
Receptor, Cannabinoid, CB1 / agonists
Receptor, Cannabinoid, CB1 / antagonists & inhibitors
Receptor, Cannabinoid, CB1 / metabolism*

Substances

Cannabinoid Receptor Agonists
Cannabinoid Receptor Antagonists
Cnr1 protein, rat
Cyclohexanols
Piperidines
Pyrazoles
Receptor, Cannabinoid, CB1
AM 251
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol