Neurochemical substrates of the rewarding effects of MDMA: implications for the development of pharmacotherapies to MDMA dependence.
Concepción Roger-Sánchez, María P García-Pardo, Marta Rodríguez‐arias, José Miñarro, María A. Aguilar
Behavioural Pharmacology April 2016 DOI: 10.1097/fbp.0000000000000210 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Rodents (animal models of reward) |
| Topics | Addiction MDMA |
| Key findings | The authors conclude that serotonin, dopamine, endocannabinoids, and endogenous opiates are the main neurotransmitter systems underlying MDMA's rewarding effects in rodents, with specific receptor subtypes and dopamine and serotonin transporters differentially involved in the acquisition, expression, extinction, and reinstatement of MDMA self-administration and conditioned place preference. They argue that extending this animal research, especially to priming-, cue-, and stress-induced reinstatement, may aid the design of new pharmacological treatments for MDMA dependence. |
Abstract
In recent years, studies with animal models of reward, such as the intracranial self-stimulation, self-administration, and conditioned place preference paradigms, have increased our knowledge on the neurochemical substrates of the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in rodents. However, pharmacological and neuroimaging studies with human participants are scarce. Serotonin [5-hydroxytryptamine (5-HT)], dopamine (DA), endocannabinoids, and endogenous opiates are the main neurotransmitter systems involved in the rewarding effects of MDMA in rodents, but other neurotransmitters such as glutamate, acetylcholine, adenosine, and neurotensin are also involved. The most important finding of recent research is the demonstration of differential involvement of specific neurotransmitter receptor subtypes (5-HT2, 5-HT3, DA D1, DA D2, CB1, μ and δ opioid, etc.) and extracellular proteins (DA and 5-HT transporters) in the acquisition, expression, extinction, and reinstatement of MDMA self-administration and conditioned place preference. It is important to extend the research on the effects of different compounds acting on these receptors/transporters in animal models of reward, especially in priming-induced, cue-induced, and stress-induced reinstatement. Increase in knowledge of the neurochemical substrates of the rewarding effects of MDMA may contribute to the design of new pharmacological treatments for individuals who develop MDMA dependence.
Comparable studies
Other preclinical and animal studies on MDMA for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study | |
| Neurotoxic Effects of MDMA on Brain Serotonin Neurons: Evidence from Neurochemical and Radioligand Binding Studiesa Rats and rhesus monkeys | 1990 | Review | |
| Enhancement of conditioned place preference response to cocaine in rats following subchronic administration of 3,4-methylenedioxymethamphetamine (MDMA) Male Sprague-Dawley rats | 2000 | Experimental study | |
| Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration Rats | 2012 | Observational cohort | |
| Profile of MDMA Self-Administration from a Large Cohort of Rats: MDMA Develops a Profile of Dependence with Extended Testing Rats | 2012 | Observational cohort | n = 128 |
Citations in the library
Cited by 6
- Oxytocin, cortisol and 3,4-methylenedioxymethamphetamine: neurohormonal aspects of recreational ‘ecstasy’ Behavioural Pharmacology December 1, 2016
- Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals. Journal of the Chinese Medical Association : JCMA May 1, 2024
- Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology British Journal of Pharmacology September 2, 2025
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Role of AMPA glutamate receptors in the conditioned rewarding effects of MDMA in mice. Behavioural Brain Research July 16, 2018
and 1 more in the library
Cites 96
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Reducedin vivobinding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users The British Journal of Psychiatry July 1, 1999
and 91 more in the library