Development and Characterization of a Novel Animal Model of Intermittent MDMA (“Ecstasy”) Exposure during Adolescence
Jerrold S. Meyer, Brian J. Piper, Valerie E. Vancollie
Annals of the New York Academy of Sciences October 1, 2008 DOI: 10.1196/annals.1432.029 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model Peer reviewed |
|---|---|
| Population | Adolescent rats |
| Intervention | MDMA |
| Dose | high doses |
| Topics | MDMA Serotonin |
| Keywords | Hallucinogen Serotonin transporter Hippocampus Impulsivity Pharmacology |
| Citations | 44 |
| Key points | Intermittent adolescent MDMA exposure causes later deficits in object-recognition memory, increased impulsivity, reduced sensitivity to a 5-HT1A agonist challenge, and reduced SERT fiber density in the hippocampus, while also inducing tolerance to a subsequent MDMA binge. |
Abstract
Adult animals treated with high doses of MDMA (“ecstasy”) either on a single day or for several consecutive days show numerous behavioral changes as well as persistent reductions in brain serotonin (5‐HT) concentrations and 5‐HT transporter (SERT) protein expression. However, such dosing regimens do not adequately mimic the intermittent use patterns commonly seen in adolescent recreational ecstasy users. We have developed and characterized a rat model of intermittent adolescent MDMA exposure that simulates many of the features of human weekend use. Animals treated with our dosing regimen experience only small increases in core body temperature, and their plasma MDMA levels compare favorably with the levels reported for heavy ecstasy users under naturalistic conditions when species differences in drug clearance rates are taken into account. Intermittent adolescent MDMA exposure causes later deficits in object‐recognition memory, increased impulsivity in the elevated plus‐maze, and reduced sensitivity to a 5‐HT 1A agonist challenge. SERT‐immunoreactive fiber density is significantly reduced in the hippocampus but not the neocortex, suggesting that the hippocampus may be particularly vulnerable to moderate MDMA exposure during adolescence. Finally, adolescent MDMA‐treated animals are protected (i.e., show tolerance) against the neurotoxic and depressant effects of a subsequent MDMA “binge” challenge. We believe that the present animal model has important clinical relevance based on the similarities between the model and the reported effects of regular ecstasy use.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 23
- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
- Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption PLoS One November 4, 2013
- Nonlinear Pharmacokinetics of (±)3,4-Methylenedioxymethamphetamine (MDMA) and Its Pharmacodynamic Consequences in the Rat Drug Metabolism and Disposition October 19, 2013
- Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA The International Journal of Neuropsychopharmacology January 11, 2013
and 18 more in the library
Cites 24
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview Journal of Psychopharmacology March 1, 2006
and 19 more in the library