Developmental Psychobiology
January 1, 2005
Brian J. Piper, Joseph B. Fraiman, Jerrold S. Meyer
71 citations
Repeated exposure to a moderate dose of MDMA during adolescence in male rats caused acute effects such as hypothermia, serotonin syndrome behavior, and ejaculation, and slowed body weight gain. Later, after the drug was stopped, the animals showed altered habituation to an open field, increased activity in an elevated plus maze, reduced attention in a novel object recognition test, and decreased serotonin transporter binding in the neocortex. These results indicate that even a moderate MDMA regimen during adolescence can produce lasting behavioral and neurochemical changes.
International Journal of Developmental Neuroscience
June 5, 2004
Jerrold S. Meyer, Mark Grande, Kenneth M. Johnson et al.
50 citations
MDMA damages fine serotonergic fibers and nerve terminals in adult organisms, while developing animals appear less susceptible, possibly due to a lack of drug-induced hyperthermia. In neonatal rats given MDMA from postnatal days 1–4, hyperthermia was produced in some groups, but all effects were independent of body temperature. The hippocampus showed significant reductions in serotonergic markers at postnatal days 25 and 60, but no effect at 9 months. However, reduced fiber density occurred in two neocortical areas, and hyperinnervation appeared in the caudate-putamen and nucleus accumbens shell. MDMA also caused a two-fold increase in cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus, indicating apoptotic cell death and long-term reorganization of forebrain serotonergic innervation. Offspring of MDMA-using women may face heightened risk for abnormal neural and behavioral development.
Journal of Neurochemistry
November 30, 2009
Dominik K. Biezonski, Jerrold S. Meyer
47 citations
MDMA (Ecstasy) causes substantial regulatory changes in serotonergic markers in rats, questioning the need to invoke distal axotomy as an explanation for MDMA-related serotonergic deficits. In adult male Sprague-Dawley rats, MDMA treatment produced large reductions in serotonin transporter (SERT) levels across all brain regions examined, but little change in vesicular monoamine transporter 2 (VMAT-2) protein expression in the hippocampus when noradrenergic input was lesioned beforehand. MDMA also caused a striking decrease in SERT gene expression and a lesser effect on VMAT-2 in raphe tissue. These findings suggest MDMA's effects involve regulatory changes rather than just nerve terminal damage.
Annals of the New York Academy of Sciences
October 1, 2008
Jerrold S. Meyer, Brian J. Piper, Valerie E. Vancollie
44 citations
Intermittent, moderate doses of MDMA given to adolescent rats, mimicking human weekend use, cause lasting memory deficits, increased impulsivity, and reduced sensitivity to a serotonin receptor challenge. Serotonin transporter fiber density decreased in the hippocampus but not the neocortex, indicating the hippocampus may be especially vulnerable. Treated animals also developed tolerance to a later MDMA binge, showing protection against neurotoxic and depressant effects. Plasma MDMA levels in the rats were comparable to those in heavy human ecstasy users when accounting for species differences in drug clearance.
Annals of the New York Academy of Sciences
August 1, 2006
Jerrold S. Meyer, Matthew E. Brevard, Brian J. Piper et al.
40 citations
A recreational dose of MDMA (1 mg/kg) activates multiple brain regions in marmoset monkeys, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit (dorsal thalamus, sensory motor cortex, and basal ganglia). MDMA also activates the primary visual cortex and enhances the visual cortical response to light. The onset of brain activation matches the rise in plasma MDMA levels. A second study found that both low (4 × 1 mg/kg oral) and high (4 × 10 mg/kg intramuscular) MDMA doses reduce the NAA/creatine ratio in the hypothalamus, indicating vulnerability to damage. High doses also cause prolonged hyperthermia and reductions in serotonin and serotonin transporters in several brain areas, suggesting even recreational doses may have adverse consequences.
Annals of the New York Academy of Sciences
June 1, 2002
Jerrold S. Meyer, Syed F. Ali
25 citations
The drug MDMA (ecstasy) damages serotonin-producing nerve fibers in adult animals, but developing animals appear less vulnerable. One hypothesis was that newborns lack the drug-induced fever that contributes to damage. This experiment tested that by inducing hyperthermia in newborn rats for two hours after each MDMA injection from postnatal day 1 to 4, while keeping other litters at normal body temperature. Even without elevated temperature, MDMA caused significant reductions in serotonin transporter binding and serotonin levels in the hippocampus by day 25, and the deficit persisted to day 60. The neocortex showed no effect at day 25 but significant damage by day 60. MDMA can damage the developing brain even without hyperthermia, and recovery may be less complete than in adults.
Developmental Psychobiology
July 1, 2014
Brian J. Piper, Christina S. Henderson, Jerrold S. Meyer
2 citations
In female rats, prior intermittent exposure to MDMA (ecstasy) prevented the drop in serotonin transporter binding and the body temperature disruption normally caused by a later high-dose MDMA binge. Unlike males, female rats did not show reduced motor activity after the binge. The findings indicate that while females and males respond differently to an MDMA binge, both sexes exhibit a preconditioning effect from earlier MDMA exposure that protects against some of the binge's harmful effects.