# Upstream CB1R Regulation of β‐Adrenergic Memory Consolidation

## TL;DR

This study shows that hippocampal CB1 receptors influence memory consolidation by interacting with beta-adrenergic signaling and BDNF.

## Contribution

The paper reveals a novel upstream regulatory mechanism of CB1Rs on βAR signaling during memory consolidation.

## Key findings

- CB1R activation impairs memory consolidation via PKA inhibition and βAR suppression.
- BDNF infusion rescues βAR antagonist-induced memory deficits.
- CB1Rs regulate memory consolidation upstream of βAR signaling through PKA and BDNF.

## Abstract

Object recognition memory (ORM) plays a key role in identifying familiar items and encoding episodic information. ORM consolidation depends on β‐adrenergic receptor (βAR) signaling and is associated with increased BDNF expression in the dorsal hippocampus. Although hippocampal activation of cannabinoid type‐1 receptors (CB1Rs) is known to impair ORM consolidation, the mechanisms underlying this effect remain unclear. In this study, we used the novel object recognition task to examine the interaction between CB1Rs and βARs during ORM consolidation in adult male Wistar rats. Intra‐dorsal CA1 infusion of the CB1R agonist ACEA, the βAR antagonist propranolol, or the PKA inhibitor myristoylated PKI14–22, administered 5‐min post‐training, impaired ORM consolidation. Notably, co‐administration of the PKA activator 8Br‐cAMP or the βAR agonist isoproterenol reversed ACEA‐induced amnesia. In contrast, the CB1R inverse agonist AM251 failed to reverse propranolol‐induced amnesia, which was instead rescued by recombinant BDNF infusion into the hippocampus 120‐min post‐training. These findings suggest that hippocampal CB1Rs regulate ORM consolidation by acting upstream of βARs via a signaling cascade involving PKA activation and BDNF expression.