Distinct morphologic classes of serotonergic axons in primates exhibit differential vulnerability to the psychotropic drug 3,4-methylenedioxymethamphetamine.
M. A. Wilson, George A. Ricaurte, M. Molliver
Neuroscience 1989 DOI: 10.1016/0306-4522(89)90237-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Normal macaque monkeys and macaques treated with (+/-)3,4-methylenedioxymethamphetamine |
| Interventions | (+/-)3 4-methylenedioxymethamphetamine |
| Topics | MDMA Serotonin |
| Key findings | MDMA produced a profound loss of serotonergic axon terminals in macaques, but the loss was selective: beaded axon terminals were largely spared while fine serotonergic axons were markedly reduced in density. Regional differences in denervation reflected the differing distributions of the two axon types in untreated animals. The authors conclude that MDMA has differential neurotoxic effects on fine and beaded serotonergic axons and hypothesize that these two classes may arise from different raphe nuclei. |
Abstract
Immunohistochemical methods were used to analyse the distribution and morphology of serotonergic axons in normal macaque monkeys and in monkeys given (+/-)3,4-methylenedioxymethamphetamine. In untreated monkeys, we observed two morphologic classes of serotonergic axon terminals, which differ in regional and laminar distribution. These two axon types, fine and beaded, correspond to the serotonergic axon types which have been described in the rat. In 3,4-methylenedioxymethamphetamine-treated monkeys, there is a profound loss of serotonergic axon terminals, yet some are consistently spared. The surviving axon terminals are nearly all of the beaded type; in contrast, fine serotonergic axons are markedly reduced in density. There are regional differences in the magnitude of denervation, which reflect differences in the distribution of these two types of serotonergic axons in controls. The present study demonstrates that 3,4-methylenedioxymethamphetamine has differential neurotoxic effects on fine and beaded serotonergic axons. These results indicate that in the primate there are two distinct classes of serotonergic axon terminals, which differ in morphology, distribution, and vulnerability to psychotropic drugs. We hypothesize that in the primate, as demonstrated in the rat, these two classes of serotonergic axon terminals may arise from different raphe nuclei. In both rodent and primate, the dorsal and median raphe nuclei give rise to parallel ascending serotonergic projections, which are likely to have different pharmacologic properties and functions.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 41
- 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
- Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Journal of Neurology, Neurosurgery, and Psychiatry June 1, 2000
- 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
- Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") Journal of Neuroscience August 1, 1995
and 36 more in the library
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
- 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. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Subjective Reports of the Effects of MDMA in a Clinical Setting Journal of Psychoactive Drugs October 1, 1986
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
and 3 more in the library