Age modulates the long-term but not the acute effects of the serotonergic neurotoxicant 3,4-methylenedioxymethamphetamine.
Journal of Pharmacology and Experimental Therapeutics October 1, 1994 DOI: 10.1016/s0022-3565(25)22778-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats at postnatal days 10, 40, and 70 |
| Interventions | 3 4-methylenedioxymethamphetamine (MDMA) |
| Duration | Time points up to 1 week after administration; acute effects assessed at ≤24 hr and ≥72 hr |
| Topics | MDMA Serotonin |
| Key findings | MDMA's biochemical effects in rat brain vary with developmental age: serotonin and 5-HIAA were persistently reduced at postnatal days 40 and 70 but not at day 10, while serotonin reuptake site populations were reduced only at day 70. Each biochemical component showed different age-dependent sensitivity to MDMA. |
Abstract
Tissue levels of serotonin (5-HT), levels of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and populations of 5-HT reuptake sites were measured in the brains of rats exposed to 3,4-methylenedioxymethamphetamine (MDMA) at selected developmental ages. MDMA exposure at postnatal day (PND) 10 did not result in altered 5-HT or 5-HIAA levels 1 week after administration in any brain region examined. However, MDMA exposure at PND 40 and PND 70 resulted in dose-dependent reductions in 5-HT and 5-HIAA levels at 1 week in all brain regions examined. Time course studies revealed that at PND 10, MDMA acutely (< or = 24 hr) reduced 5-HT levels and that these levels later recovered to control levels. MDMA also acutely reduced 5-HT levels at PND 40 and PND 70, but at these ages the 5-HT levels were persistently depressed ( > or = 72 hr). Time course studies also revealed that MDMA acutely elevated dopamine levels in caudate putamen at PND 40 and PND 70, but no alterations in dopamine levels were observed at PND 10. Analysis of 5-HT reuptake site populations revealed that at PND 10 and PND 40, MDMA had little effect on reuptake site populations. At PND 70, however, MDMA reduced 5-HT reuptake site populations as early as 24 hr after administration. These experiments demonstrate not only that the biochemical effects of MDMA exposure are altered by the developmental status of the experimental animal, but also that each individual biochemical component may show differing sensitivities to alteration by MDMA at different developmental ages.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 23
- A study of the neurotoxic effect of MDMA (‘ecstasy’) on 5‐HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy British Journal of Pharmacology June 1, 1997
- 3,4-Methylenedioxymethamphetamine (Ecstasy)-Induced Learning and Memory Impairments Depend on the Age of Exposure during Early Development Journal of Neuroscience May 1, 2001
- Dopaminergic mechanisms of reinstatement of MDMA‐seeking behaviour in rats British Journal of Pharmacology December 30, 2010
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats International Journal of Developmental Neuroscience June 5, 2004
and 18 more in the library