(±)3,4-methylenedioxymethamphetamine ("ecstasy") treatment modulates expression of neurotrophins and their receptors in multiple regions of adult rat brain.
Ann M. Hemmerle, Jonathan W. Dickerson, Nicole R Herring, Tori L. Schaefer, Charles V. Vorhees, Michael T. Williams, Kim B. Seroogy
The Journal of Comparative Neurology August 1, 2012 DOI: 10.1002/cne.23048 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Intervention | MDMA |
| Dose | 10 mg/kg × 4 at 2-hour intervals on a single day |
| Duration | Brains examined 1, 7, or 24 hours after the last dose |
| Measures | in situ hybridization with cRNA probes for BDNF, NT-3, trkB, and trkC mRNA |
| Topics | MDMA |
| Keywords | Substantia nigra Hippocampus Neostriatum Cerebral cortex Animals Rats, sprague-dawley N-methyl-3,4-methylenedioxyamphetamine Corticosterone Tyrosine 3-monooxygenase Receptor, trkb Receptor, trkc Brain-derived neurotrophic factor Neurotrophin 3 Rna, messenger Serotonin agents Hallucinogens Body temperature Random allocation Time factors Male |
| Citations | 29 |
| Key findings | A serotonin-depleting regimen of MDMA (10 mg/kg four times at 2-hour intervals) upregulated BDNF, NT-3, trkB, and trkC messenger RNA in multiple rat brain regions, most prominently the prefrontal cortex, with additional region-specific increases in cortical, nigrostriatal, and hippocampal areas. The authors suggest these changes in neurotrophin signaling may play a role in the learning and memory deficits seen after MDMA treatment. |
Abstract
(±)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high-affinity receptors, tropomyosin receptor kinase (trk)B and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg × 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats, and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB, and trkC were analyzed by using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB, and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased NT-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta, and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in the learning and memory deficits seen following MDMA treatment.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 15
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & Behavior February 1, 2019
- Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction. Journal of Neuroscience Research April 1, 2022
- MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2024
- Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies. Frontiers in Pain Research April 19, 2024
and 10 more in the library
Cites 14
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Journal of Neurology, Neurosurgery, and Psychiatry June 1, 2000
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Human Research on MDMA (3,4-Methylene- dioxymethamphetamine) Neurotoxicity: Cognitive and Behavioural Indices of Change Neuropsychobiology 2000
- Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT Synapse 2001
and 9 more in the library