# Involvement of Adenosine A2A Receptors in Anxiety‐Like Behaviors in Tetrahydrocannabinol‐Treated Mice

## TL;DR

This study explores how adenosine A2A receptors influence anxiety-like behaviors in mice treated with THC, revealing interactions between adenosinergic and cannabinoid systems.

## Contribution

The study identifies a novel interaction between adenosinergic and cannabinoid systems in modulating anxiety-like behaviors in THC-treated mice.

## Key findings

- THC induces anxiety-like behavior in mice.
- THC's effects are partially modulated by changes in CB1R and A2AR receptor expression.
- Behavioral and molecular data suggest cross-talk between adenosinergic and cannabinoid systems.

## Abstract

Previous studies have suggested that adenosinergic system in the central nervous system may play a role in both behavioral changes and the physiopathology induced by Δ9‐tetrahydrocannabinol (THC), and this is thought to be mediated by adenosine A2A receptors (A2ARs). However, the contribution of the adenosinergic system to the anxiety‐like behaviors in response to THC in mice is not well understood.

In this study, we aimed to investigate the possible role of the adenosinergic system in THC‐treated mice.

For that purpose, we combined behavioral tests and molecular analyses to investigate the effects of THC in relation with the agonist and antagonist of the adenosinergic system, CGS‐21680 (CGS) and istradefylline, respectively, on both anxiety‐like behaviors and hippocampal gene expression.

The results demonstrated that THC induced anxiety‐like behavior, and gene expression patterns indicated a significant interaction between the adenosinergic and cannabinoidergic systems. Notably, the data suggest that THC plays a predominant role in this molecular interplay, with its effects being partially modulated by changes in the expression of both cannabinoidergic and adenosinergic receptors, CB1R and A2AR, respectively.

These findings contribute to the understanding of THC's complex pharmacological actions, highlighting the importance of receptor cross talk in modulating anxiety and other behavioral outcomes.

This study evaluated anxiety‐like behavior in mice across treatment and control groups using open field and elevated plus maze tests, followed by hippocampal receptor gene expression analysis. The combined behavioral and molecular data identify potential receptor‐level mechanisms underlying the observed treatment‐associated behavioral changes.