Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice.
Konstantin Kuteykin-Teplyakov, Rafaël Maldonado
European Neuropsychopharmacology November 2014 DOI: 10.1016/j.euroneuro.2014.08.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | MDMA WAY-100635 L-368899 |
| Dose | 3 mg/kg |
| Topics | MDMA |
| Keywords | 4-methylenedioxyamphetamine 5-ht1a receptor N-methyl-3 Oxytocin Proteomics Social behavior |
| Key findings | Low-dose MDMA (3 mg/kg) had differential effects on mouse social behavior: some mice showed increased sociability without hyperlocomotion, while others showed hyperlocomotion without increased sociability. Both the 5-HT1A antagonist WAY-100635 and the oxytocin receptor antagonist L-368899 abolished the prosocial effect. Proteomic analysis linked 21 proteins to sociability and suggested roles for GABA B receptor neurotransmission and energy maintenance. |
Abstract
Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3,4-methylenedioxyamphetamine (MDMA, "Ecstasy") at low dose (3mg/kg) has differential effects on mouse social behavior. In some animals, MDMA promotes sociability without hyperlocomotion, whereas in other mice it elevates locomotor activity without affecting sociability. Both WAY-100635, a selective antagonist of 5-HT1A receptor, and L-368899, a selective oxytocin receptor antagonist, abolish prosocial effects of MDMA. Differential quantitative analysis of brain proteome by isobaric tag for relative and absolute quantification technology (iTRAQ) revealed 21 specific proteins that were highly correlated with sociability, and allowed to distinguish between entactogenic prosocial and hyperlocomotor effects of MDMA on proteome level. Our data suggest particular relevance of neurotransmission mediated by GABA B receptor, as well as proteins involved in energy maintenance for MDMA-induced sociability. Functional association network for differentially expressed proteins in cerebral cortex, hippocampus and amygdala were identified. These results provide new information for understanding the neurobiological substrate of sociability and may help to discover new therapeutic approaches to modulate social behavior in patients suffering from social fear and low sociability.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- Separating the agony from ecstasy: R(−)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice Neuropharmacology October 6, 2017
- The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish Frontiers in Psychiatry August 13, 2017
- Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD. Pharmaceuticals June 27, 2024
- Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis). PLoS One June 11, 2016
- History, pharmacology and therapeutic mechanisms of 3,4‐methylenedioxymethamphetamine (MDMA) British Journal of Pharmacology October 21, 2025
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