Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa
- 1 October 1990
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 600 (1), 640-661
- https://doi.org/10.1111/j.1749-6632.1990.tb16916.x
Abstract
The cytotoxic effects of amphetamine derivatives were studied by immunocytochemistry to identify the cellular compartments affected by these drugs, to obtain morphologic evidence of neuronal degeneration, and to assess the potential for regeneration. The substituted amphetamines, MDA, MDMA, PCA, and fenfluramine, all release serotonin and cause acute depletion of 5-HT from most axon terminals in forebrain. (1) Unequivocal signs of axon degeneration were seen at 36-48 hour survivals: 5-HT axons exhibited increased caliber, huge, swollen varicosities, fragmentation, and dilated proximal axon stumps. (2) Fine 5-HT axon terminals were persistently lost after drug administration, while beaded axons and raphe cell bodies were spared. These two types of 5-HT axons, which arise from separate raphe nuclei and form distinct ascending projections, are differentially vulnerable to psychotropic drugs. (3) From 2-8 months after treatment, there was progressive serotonergic re-innervation of neocortex along a fronto-occipital gradient. Longitudinal 5-HT axons grew into layers I and VI from rostral to caudal, before sprouting into middle cortical layers; this bilaminar pattern of growth simulates perinatal development of 5-HT innervation. This study demonstrates differential vulnerability of 5-HT projections, evidence for axonal degeneration, and sprouting of 5-HT axons leading to re-innervation of forebrain. While the sprouting axons are anatomically similar to the type that was damaged, it is not known whether a normal pattern of innervation is re-established.This publication has 43 references indexed in Scilit:
- Anatomic evidence for a neurotoxic effect of (±)-fenfluramine upon serotonergic projections in the ratBrain Research, 1990
- Uneven Pattern of Dopamine Loss in the Striatum of Patients with Idiopathic Parkinson's DiseaseNew England Journal of Medicine, 1988
- Serotoninergic innervation of the cat cerebral cortexJournal of Comparative Neurology, 1988
- Serotonergic Neuronal SystemsJournal of Clinical Psychopharmacology, 1987
- The organization of divergent axonal projections from the midbrain raphe nuclei in the ratJournal of Comparative Neurology, 1986
- The serotonin and norepinephrine innervation of primary visual cortex in the cynomolgus monkey (Macaca fascicularis)Journal of Comparative Neurology, 1984
- An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the ratJournal of Comparative Neurology, 1978
- Connections of the median and dorsal raphe nuclei in the rat: An autoradiographic and degeneration studyJournal of Comparative Neurology, 1974
- Ascending Monoamine Neurons to the Telencephalon and DiencephalonActa Physiologica Scandinavica, 1966
- The Distribution of Adrenergic Nerve Fibres to the Blood Vessels in Skeletal MuscleActa Physiologica Scandinavica, 1965