The A2a adenosine receptor modulates the reinforcement efficacy and neurotoxicity of MDMA
Jéssica Ruiz‐medina, Catherine Ledent, Olga Carretón, Olga Valverde
Journal of Psychopharmacology January 24, 2011 DOI: 10.1177/0269881110389210 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with knockout mice Peer reviewed |
|---|---|
| Population | A2a adenosine receptor knockout mice and wild-type littermates |
| Intervention | MDMA |
| Topics | MDMA |
| Keywords | Neurotoxicity Adenosine a2a receptor Pharmacology Adenosine receptor Knockout mouse Astrogliosis Neuroinflammation Striatum Dopamine |
| Citations | 33 |
| Post-publication review | 1 comment on PubPeer (opens in new tab) · last active September 2016 |
| Key findings | A2a adenosine receptors are essential for MDMA reinforcement and striatal neuroinflammation, as their absence abolishes self-administration and attenuates glial activation. |
Abstract
Adenosine is an endogenous purine nucleoside that plays a neuromodulatory role in the central nervous system. A2a adenosine receptors have been involved in reward-related processes, inflammatory phenomena and neurotoxicity reactions. In the present study, we investigated the role of A2a adenosine receptors on the acute pharmacological effects, reinforcement and neuroinflammation induced by MDMA administration. First, the acute effects of MDMA on body temperature, locomotor activity and anxiety-like responses were measured in A2a knockout mice and wild-type littermates. Second, MDMA reinforcing properties were evaluated using the intravenous self-administration paradigm. Finally, we assessed striatal astrogliosis and microgliosis as markers of MDMA neurotoxicity. Our results showed that acute MDMA produced a biphasic effect on body temperature and increased locomotor activity and anxiogenic-like responses in both genotypes. However, MDMA reinforcing properties were dramatically affected by the lack of A2a adenosine receptors. Thus, wild-type mice maintained MDMA self-administration under a fixed ratio 1 reinforcement schedule, whereas the operant response appeared completely abolished in A2a knockout mice. In addition, the MDMA neurotoxic regime produced an enhanced inflammatory response in striatum of wild-type mice, revealed by a significant increase in glial expression, whereas such activation was attenuated in mutant mice. This is the first report indicating that A2a adenosine receptors play a key role in reinforcement and neuroinflammation induced by the widely used psychostimulant.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice Behavioural Pharmacology September 1, 2014
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications Pharmaceuticals June 17, 2011
- Increased response to 3,4 methylenedioxymethamphetamine (MDMA) reward and altered gene expression in zebrafish during short- and long-term nicotine withdrawal Molecular Neurobiology November 24, 2020
and 5 more in the library
Cites 13
- Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacology March 3, 2006
- Human Pharmacology of 3,4-Methylenedioxymeth-amphetamine ("Ecstasy"): Psychomotor Performance and Subjective Effects Journal of Clinical Psychopharmacology August 1, 2000
- RETRACTED: Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ("Ecstasy") Science September 27, 2002
- Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice British Journal of Pharmacology October 29, 2003
- Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Pharmacology 2001
and 8 more in the library