Involvement of Adenosine A2A Receptors in Anxiety-Like Behaviors in Tetrahydrocannabinol-Treated Mice.
Burçin Ün, Zeki Akarsakarya, Özlem Yorulmaz Özü, Nermin Seda Ilgaz, Mehmet Bertan Yılmaz, Deniz Seçilmiş, Mehmet Ata Seçilmiş
Brain and Behavior February 1, 2026 DOI: 10.1002/brb3.71126 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | THC CGS-21680 istradefylline |
| Topics | Cannabis Anxiety |
| Keywords | Adenosine a2a receptors Anxiety‐like behaviors Hippocampus |
| Key findings | THC induced anxiety-like behavior, and gene expression patterns indicated a significant interaction between the adenosinergic and cannabinoidergic systems, with THC playing a predominant role in this molecular interplay. |
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
-
THC induced anxiety-like behavior, with adenosinergic and cannabinoidergic receptor systems interacting in this effect.
Synthesized
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.
Citations in the library
Cites 8
- Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties Journal of Translational Medicine October 2, 2020
- Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Psychopharmacology October 13, 2022
- Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats. Psychopharmacology July 2017
- Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology November 2011
- Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress. Journal of Psychopharmacology May 2010
and 3 more in the library