Serotonergic recovery after (+/-)3,4-(methylenedioxy) methamphetamine injury: observations in rats.
C R Scanzello, George Hatzidimitriou, A L Martello, J L Katz, George A. Ricaurte
Journal of Pharmacology and Experimental Therapeutics March 1, 1993 DOI: 10.1016/s0022-3565(25)10168-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study (controlled time-course experiment in rats) Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Male Sprague-Dawley rats, including MDMA-treated groups and age-matched controls |
| Intervention | MDMA |
| Dose | 10 mg/kg i.p. every 2 hr for a total dose of 40 mg/kg |
| Duration | Follow-up at 2, 8, 16, 32, and 52 weeks after MDMA treatment |
| Measures | Regional brain 5-HT, 5-hydroxyindoleacetic acid, [3H]paroxetine-labeled 5-HT uptake sites, immunohistochemistry |
| Topics | Serotonin |
| Keywords | Neurons Axons Animals Rats, sprague-dawley N-methyl-3,4-methylenedioxyamphetamine Hydroxyindoleacetic acid Paroxetine Immunohistochemistry Brain chemistry Male |
| Key findings | Two weeks after MDMA, serotonin neuronal markers were reduced by 42 to 82% depending on brain region. Recovery was evident in some regions by 16 weeks and nearly complete in most by 32 weeks, and still evident at one year. However, a few rats showed severe, enduring serotonergic deficits in multiple brain regions, so recovery was not universal. |
Abstract
(+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug of abuse which damages serotonin (5-HT) neurons in animals. In monkeys, the damage appears to be permanent. By contrast, in rats there is indication that neuronal recovery takes place, although there is question as to whether the recovery is sustained. The purpose of the present study was to examine the fate of 5-HT neurons in MDMA-treated rats, and to compare findings in the rat with those in the monkey. Rats were treated with MDMA (10 mg/kg i.p.) every 2 hr for a total dose of 40 mg/kg. Two, 8, 16, 32 and 52 weeks later, groups (n = 8) of MDMA-treated rats, along with age-matched controls (n = 8), were analyzed for regional brain 5-HT, 5-hydroxyindoleacetic acid and [3H]paroxetine-labeled 5-HT uptake sites. Two weeks after MDMA, 5-HT neuronal markers were reduced markedly. Reductions ranged from 42 to 82% depending on brain region. By 16 weeks, there was evidence of recovery in some brain regions (e.g., hypothalamus and striatum) and by 32 weeks, recovery was nearly complete in most brain regions examined. One year after MDMA, recovery was still evidence in all brain regions evaluated, although closer inspection of the group data revealed that whereas most MDMA-treated rats recovered, some did not. These few animals had severe and enduring serotonergic deficits in multiple brain regions. Morphologic immunocytochemical studies yielded results which corroborated the neurochemical findings.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 54
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
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