Methylenedioxyamphetamine: neurotoxic effects on serotonergic projections to brainstem nuclei in the rat.
John A. Harvey, S E McMaster, A G Romano
Brain Research August 13, 1993 DOI: 10.1016/0006-8993(93)91590-o (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Animals (species not stated) assigned to saline, MDA, or fluoxetine-plus-MDA groups |
| Interventions | Methylenedioxyamphetamine hydrochloride (MDA) Fluoxetine hydrochloride |
| Dose | MDA 40 mg/kg/day; fluoxetine 10 mg/kg |
| Duration | Twice daily injections for 4 consecutive days |
| Measures | 5-HT immunocytochemistry |
| Topics | Serotonin |
| Key findings | MDA (40 mg/kg/day for 4 days) caused a pronounced loss of 5-HT immunoreactivity in forebrain and an equally severe loss in brainstem regions such as the superior colliculus, superior olivary complex, trigeminal sensory complex and vestibular nuclei, with fine axon terminals relatively absent. Prior fluoxetine (10 mg/kg) completely blocked these effects. The authors suggest the brainstem denervation could alter visually guided eye movements, the vestibulo-ocular reflex, and tactual reflexes. |
Abstract
This study employed immunocytochemistry to visualize the neurotoxic effects of methylenedioxyamphetamine hydrochloride (MDA) on serotonergic projections to brainstem structures. Separate groups of animals were injected twice a day, for 4 consecutive days, with: saline; MDA (40 mg/kg/day); or fluoxetine hydrochloride (10 mg/kg) prior to each injection of MDA. In agreement with previous reports, MDA produced a pronounced loss of 5-HT immunoreactivity in the forebrain, most notably in neocortex and hippocampus. However, our results revealed that MDA also produced a loss of 5-HT fibers in brainstem that was as severe as that seen in any region of forebrain. Regions most severely affected included: superior colliculus; superior olivary complex; trigeminal sensory complex and vestibular nuclei. The brains of animals treated with MDA demonstrated a relative absence of fine 5-HT axon terminals within these forebrain and brainstem regions, while thicker axonal elements were still present. The neurotoxic effects of MDA on serotonergic projections to forebrain and brainstem were completely blocked by the prior administration of the 5-HT reuptake inhibitor, fluoxetine. It was suggested that the denervation of the superior colliculus, superior olive and vestibular nuclei could alter visually guided eye movements and the vestibulo-ocular reflex while the loss of serotonergic inputs to the trigeminal sensory complex might be expected to alter tactual reflexes.
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 3
- The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype British Journal of Pharmacology August 1, 1995
- The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacological Reviews September 2003
- Methylenedioxyamphetamine: a selective effect on cortical content and turnover of 5-HT. Pharmacology, Biochemistry, and Behavior November 1994
Cites 8
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Enhanced learning following a single, acute dose of MDA. Pharmacology, Biochemistry, and Behavior April 1993
and 3 more in the library