Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")
Christina Weide Fischer, George Hatzidimitriou, J Wlos, Jonathan L. Katz, George A. Ricaurte
Journal of Neuroscience August 1, 1995 DOI: 10.1523/jneurosci.15-08-05476.1995 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats and squirrel monkeys |
| Intervention | MDMA |
| Duration | 12-18 months post-lesion |
| Topics | MDMA Serotonin |
| Keywords | Recreational drug Hallucinogen Pharmacology 5-HT Receptor |
| Citations | 269 |
| Key points | MDMA injury leads to lasting reorganization of serotonin axon projections, with some brain regions remaining denervated and others reinnervated or hyperinnervated. |
Abstract
The recreational drug (+/)3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) is a methamphetamine derivative that selectively destroys central 5-HT axons and axon terminals in animals and, possibly, humans. The fate of 5-HT neurons following MDMA injury is uncertain. In particular, while it is known that central 5-HT axons can undergo regenerative sprouting after MDMA injury, it has not been determined whether they reestablish the original innervation pattern. To address this question, the present studies examined 5-HT innervation patterns in animals lesioned with MDMA 12–18 months previously. Both rodents (rats) and nonhuman primates (squirrel monkeys) were examined, since there is indication that serotonergic recovery after MDMA injury may be species dependent. 5-HT axon projections were studied neurochemically, autoradiographically and immunocytochemically. In both rodents and nonhuman primates previously lesioned with MDMA, substantial serotonergic axonal sprouting was observed. However, in a few rats and in most squirrel monkeys, the reinnervation pattern was highly abnormal: distant targets (e.g., dorsal neocortex) remained denervated, while some proximal targets (e.g., amygdala, hypothalamus) were reinnervated or hyperinnervated. Although the specific determinants of axonal recovery after MDMA injury remain to be identified, it appears that axons which initially sustain more severe damage, are longer, or are more highly arborized have low probability of recovering. The observation that some brain regions remain denervated, while others are reinnervated or hyperinnervated suggests that, under some circumstances, MDMA injury can lead to a lasting reorganization of ascending 5-HT axon projections. Such lasting changes in brain innervation, documented here in MDMA-treated animals, may have implications for humans using MDMA recreationally.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 96
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- 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 (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
and 91 more in the library
Cites 10
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug British Journal of Addiction August 1, 1992
- MDMA: Nonmedical Use and Intoxication Journal of Psychoactive Drugs October 1, 1986
- Increasing Use of “Ecstasy“ (MDMA) and other Hallucinogens on a College Campus Journal of American College Health May 1, 1994
- MDMA: Its History and Pharmacology Psychiatric Annals March 1, 1994
and 5 more in the library