Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers.
Rubén García‐cabrerizo, M Julia García-Fuster
Neurotoxicology July 2015 DOI: 10.1016/j.neuro.2015.06.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent (postnatal day 37) and young adult (postnatal day 58) rats |
| Intervention | MDMA |
| Dose | 3×5 mg/kg, i.p., every 2 h |
| Duration | One or four days of MDMA administration |
| Topics | MDMA Neuroplasticity |
| Keywords | Adolescence Fadd Hippocampus |
| Key findings | Four days of binge-pattern MDMA in adolescent and young adult rats reduced hippocampal serotonergic and GABAergic signaling proteins and structural neurofilament proteins without increasing apoptosis; instead, pro-apoptotic proteins (FADD, Bax, cytochrome c) and cell-death markers were inhibited, which the authors propose may be a compensatory response to MDMA-induced protein deficits. |
Abstract
While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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- The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research Behavioural Brain Research February 10, 2026
- The role of 5-HT1A and 5-HT1B receptors in MDMA self-administration 2016
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Cites 13
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- 3,4‐methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein Synapse July 14, 2004
- Repeated MDMA (“Ecstasy”) exposure in adolescent male rats alters temperature regulation, spontaneous motor activity, attention, and serotonin transporter binding Developmental Psychobiology 2005
- MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase Journal of Neuroimmune Pharmacology November 17, 2012
- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
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