The entactogen MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") disrupts helping behaviour while reinforcing electrophysiological indicators of potentially associated synaptic plasticity in male Sprague-Dawley rats.
Patricio Sáez-briones, Amanda Silva-Rodríguez, Michelle Morales-Vidal, Yaniz Sepúlveda-fernández, Dorys Jara-Clen, Michelle Castro-Choapa, Pablo Livacic-Rojas, Darío Martínez-afani, Bruce K. Cassels, Rafael Barra, Luis Constandil, Jeffri Retamal, Alejandro Hernández
Frontiers in Pharmacology 2026 DOI: 10.3389/fphar.2026.1779772 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult male rats |
| Intervention | MDMA (3 |
| Dose | 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, and 10 mg/kg i.p. |
| Topics | Serotonin MDMA Neuroplasticity |
| Keywords | 3,4-methylenedioxymethamphetamine Helping behaviour Oxytocin |
| Key findings | MDMA suppressed helping behavior in rats at higher doses (5 mg/kg and 10 mg/kg) while enhancing neuroplasticity in brain regions linked to prosocial behavior. |
Abstract
In humans, empathy is expressed through various prosocial behaviours between individuals that may be enhanced after intake of the synthetic entactogen MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") as the behavioural expression of the so-called entactogenic syndrome. Rodents may also exhibit empathy-like behaviours, such as social interaction and helping behaviour. In this regard, while social interaction has been reported to be enhanced by MDMA, the effects of this drug on helping behaviour remain unexplored. Nevertheless, because helping behaviour is considered as part of the prosocial repertoire, it may be hypothesised that MDMA should enhance it. In the present study, the evaluation of a subtoxic dose range (0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, and 10 mg/kg i.p.) of MDMA on helping behaviour in adult male rats has been conducted using a standardised behavioural setup based on the intrinsic aversion of these animals to water. In addition, as helping behaviour may require a complex interaction between motivational and higher cognitive processes, the neuroplastic effects of MDMA (10 mg/kg i.p.) on cortical and subcortical loci were studied in vivo in anaesthetised rats. Behavioural data indicated that 5 mg/kg and 10 mg/kg of MDMA fully suppressed helping behaviour; 1 mg/kg and 0.5 mg/kg induced partial inhibition only after interchanging roles; and 0.25 mg/kg had no effect. The inhibitions observed at the highest doses (5 mg/kg, and 10 mg/kg) were not reversed after interchanging roles. Electrophysiological data showed that MDMA reinforced long-term depression (LTD) elicited in the nucleus accumbens (NAc) core following stimulation of the dorsal raphe nucleus (DRN). In addition, MDMA increased transcallosal-evoked long-term potentiation (LTP) in the anterior cingulate cortex (ACC) in a serotonin (5-HT)- and oxytocin (OXT)-dependent manner. Taken together, these data support the notion that MDMA disrupts helping behaviour, even though the neuroplastic effects elicited by the drug align with the mechanisms described to promote prosocial/empathic behaviours. The results may suggest a negative modulation of MDMA on neural processes that are essential for the execution of helping behaviour without affecting the willingness to help.
Comparable studies
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| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cites 21
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
- Oxytocin-dependent reopening of a social reward learning critical period with MDMA Nature April 3, 2019
- The Prosocial Effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled Studies in Humans and Laboratory Animals Neuroscience & Biobehavioral Reviews September 25, 2015
- Distinct neural mechanisms for the prosocial and rewarding properties of MDMA Science Translational Medicine December 11, 2019
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
and 16 more in the library