Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part I: Synaptosomal uptake and tissue concentrations.
K E Sabol, R Lew, J B Richards, Georgetta Vosmer, Lewis S. Seiden
Journal of Pharmacology and Experimental Therapeutics February 1, 1996 DOI: 10.1016/s0022-3565(25)12371-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Rats (Sprague-Dawley) |
| Intervention | MDMA |
| Dose | 20 mg/kg, 8 times at 12-hr intervals |
| Duration | 52-week posttreatment period; measurements at 2, 8, 16, 32, or 52 weeks after treatment |
| Measures | synaptosomal uptake of 3H-5-HT and 3H-DA, tissue concentrations of dopamine and 5-HT |
| Topics | Serotonin MDMA |
| Keywords | Synaptosomes Animals Rats, sprague-dawley Dopamine N-methyl-3,4-methylenedioxyamphetamine Serotonin agents Brain chemistry Time factors Male |
| Key findings | A high-dose MDMA regimen in rats caused long-lasting serotonin depletions that recovered at different rates depending on brain region. Frontal-parietal cortex, occipital-temporal cortex, and hippocampus showed the least recovery, with significant depletions still present 52 weeks after treatment, whereas hippocampal synaptosomal serotonin uptake had returned to normal by 16 weeks. |
Abstract
The effects of a high dose methylenedioxymethamphetamine (MDMA) regimen on the serotonin (5-HT) system were evaluated over a 52-wk period. MDMA was administered to rats (20 mg/kg) 8 times at 12-hr intervals. Tissue concentrations of dopamine (DA) and 5-HT, and synaptosomal uptake of 3H-5-HT and 3H-DA were measured at 2, 8, 16, 32 or 52 wk posttreatment. Synaptosomal uptake of 3H-5-HT (hippocampus) was decreased at 2 and 8 wk, but not at 16, 32 or 52 wk after drug. 5-HT tissue concentrations were measured in frontal cortex, frontal-parietal cortex, occipital-temporal cortex, nucleus accumbens/olfactory tubercle, striatum, amygdala, hippocampus, septum, hypothalamus, ventral tegmentum/substantia nigra. Two weeks after MDMA treatment, all regions showed decreased 5-HT tissue concentrations except septum. Recovery over the 52-wk interval was noted for all depleted regions, but the rate and degree of recovery was region dependent. Frontal-parietal cortex, occipital-temporal cortex and hippocampus showed the least recovery, with significant depletions at 52 wk posttreatment. Hypothalamus showed an increase in 5-HT tissue concentrations relative to age-matched controls at 52 wk. These results indicate that a high-dose MDMA regimen results in long-lasting depletions of serotonin. The rate and degree of recovery of serotonin tissue concentrations seen over the 52-wk test period is region specific.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
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