The Journal of Comparative Neurology
January 1, 2006
Csaba Ádori, Rómeó D. Andó, Gábor G. Kovács et al.
51 citations
MDMA (ecstasy) causes lasting damage to the brain's serotonin system. In Dark Agouti rats, a single injection of MDMA at doses of 7.5, 15, or 30 mg/kg reduced the density of serotonin-producing axons throughout the brain 3 and 7 days later. Three days after treatment, a dose-dependent increase in the stress protein Hsp27 appeared in star-shaped glial cells (astrocytes) in several cortical areas and the hippocampus CA1 region, but not in other brain regions like the caudate putamen. The hippocampus CA1 showed both increased Hsp27 and another marker of glial activation (GFAP), suggesting particular vulnerability. High-dose MDMA also triggered Hsp72 in neurons, indicating effects beyond serotonin cells.
International Journal of Neuropsychopharmacology
September 25, 2023
Szabolcs Koncz, Noémi Papp, Dóra Pothorszki et al.
29 citations
Racemic ketamine contains two mirror-image molecules, (R)-ketamine and (S)-ketamine, which have different effects. (S)-ketamine is approved for treating major depression, but (R)-ketamine failed in recent clinical trials. In rats, a single dose of (S)-ketamine, but not (R)-ketamine, delayed the onset of rapid eye movement (REM) sleep, reduced total REM sleep time, and increased slow-wave activity during non-REM sleep. (S)-ketamine also increased wakefulness and decreased non-REM sleep in the first two hours. In chronically stressed rats, only (S)-ketamine reduced immobility in the forced swimming test, indicating antidepressant-like activity. The two enantiomers produce markedly different effects on sleep-wake patterns and behavior at the same dose.
The International Journal of Neuropsychopharmacology
August 1, 2005
Eszter Kirilly, Anita Benkő, Linda Ferrington et al.
26 citations
A single dose of MDMA (15 mg/kg) in male Dark Agouti rats caused lasting damage to the serotonin system, shown by 30–60% reductions in paroxetine binding in the forebrain and decreased brain glucose metabolism in aggression-related areas. Despite this neurotoxicity, aggressive behaviors (biting, boxing, wrestling) were not significantly different from controls three weeks later, and the acute anti-aggressive effects of MDMA and two 5-HT1B receptor agonists remained intact. The findings suggest that aggressive behavior and the acute anti-aggressive action of MDMA are preserved even with substantial serotonergic damage, at least under the social isolation conditions of the resident-intruder test.
European Journal of Neuroscience
July 1, 2006
Linda Ferrington, Eszter Kirilly, Douglas E. Mcbean et al.
21 citations
A single dose of MDMA causes long-term loss of serotonin nerve terminals and disrupts the normal coupling between brain blood flow and glucose use. Three weeks after MDMA pretreatment in rats, serotonin transporter density fell by about 46% and paroxetine binding by 47%. Brain glucose use decreased widely, but blood flow did not change, indicating lost cerebrovascular constrictor tone. A subsequent MDMA dose increased glucose use but decreased blood flow overall; in half of pretreated rats, random focal hyperemia suggested a failure of autoregulation during MDMA-induced hypertension. The findings suggest that prior MDMA exposure does not protect against acute cerebrovascular dysfunction and may, in some individuals, increase stroke risk.
Pharmaceuticals (Basel, Switzerland)
February 1, 2024
Dóra Pothorszki, Szabolcs Koncz, Dóra Török et al.
7 citations
In rats, (R)-ketamine, but not (S)-ketamine, dose-dependently increases EEG theta power during wakefulness and REM sleep for 23 hours. Theta rhythm originates in the hippocampus and is linked to cognitive functions, attention, and decreased anxiety. This effect on a hippocampal function not affected by (S)-ketamine may relate to neural plasticity and memory encoding.
British journal of pharmacology
June 1, 2026
Szabolcs Koncz, Dóra Pothorszki, Noémi Papp et al.
2 citations
In rats, the (S)-enantiomer of ketamine (esketamine) produces a fourfold stronger wake-promoting effect and a twofold stronger increase in gamma brainwave power during wakefulness compared to the (R)-enantiomer (arketamine). Only esketamine enhances delta power during NREM sleep after gamma activity normalizes, a pattern called the gamma-delta shift. This shift, previously proposed as a marker of antidepressant activity for racemic ketamine, appears specific to esketamine. The findings help clarify which enantiomer drives the EEG changes and suggest that the gamma-delta shift may serve as a biomarker for antidepressant effects, relevant to treatment-resistant depression.