Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a popular party drug known to cause selective serotonergic damage. Here we examined the long-term recovery and aging of serotonergic fibers and levels of brain-derived neurotrophic factor (BDNF) after intermittent MDMA administration (15 mg kg(-1) i.p. every 7th day for 4 weeks, MDMA ×4) and a single-dose treatment (15 mg kg(-1) i.p., MDMA ×1) in adolescent/young adult male Dark Agouti rats. After MDMA treatment, tryptophan hydroxylase-immunoreactive fiber density decreased and then recovered in all brain regions. Recovery was more pronounced in the MDMA ×4 group compared with the MDMA ×1 group, but similar long-term BDNF responses were found after both treatments. Twenty-two months after treatment, there were fewer clusters of aberrant serotonergic fibers in the parietal cortex in the MDMA ×4 group compared with the MDMA ×1 group. There was no difference in the density of microglial cells or astrocytes in treated groups versus the control 22 months after the treatments. These results indicate that recovery of serotonergic fibers is faster after intermittent MDMA treatment than after single-dose administration, and differences in BDNF levels per se are unlikely to account for this difference. Moreover, it seems that intermittent MDMA treatment attenuates the morphological signs of aging in serotonergic fibers. In addition, neither intermittent nor single-dose MDMA exposition of young animals induces accelerated aging processes or neurodegeneration in senescence, as indicated by the unaltered densities of microglial cells and astrocytes in the treated groups compared with the control.

Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease

“…Such features have already been reported for serotonergic and cholinergic systems in normal, aging rats [7,110,77,3], as well as in the entire monoaminergic system of Zitter mutant or microenchephalic rats [106,114]. Enlarged/swollen varicosities are generated by accumulations of intra-axonal materials as a result of impaired axonal transport due to destabilization of microtubules.…”

“…connections' and 'aberrant fiber clusters'/mm 2 were determined in unilateral fronto-parietal cortices as described before [3]. A detailed description of these aberrant structures is reported in the Results and Fig.…”

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

“…Recent studies have shown that MDMA chronically inhibits neocortical serotonin signaling in parallel with hyperthermia345 and causes deficits in prospective memory and/or social intelligence6. Animal studies have demonstrated that repeated administration of MDMA results in clusters of aberrant serotonergic fibers7 and affects the serotonergic neurotransmitter system in an association with reduced density of cerebral serotonin transporters (SERT) in the brain89. Regarding serotonergic pathway of brain, MDMA alters serotonin (5-HT), 5-HT receptors, and SERT levels910.…”

Psychiatric profiles of mothers who take Ecstasy/MDMA during pregnancy: Reduced depression 1 year after giving birth and quitting Ecstasy

“…Because the positive mood intensification under MDMA is brief (several hours), and the post-MDMA period of mood recovery is more prolonged (several days), the average weekly mood of Ecstasy users will often be lower than in non-users (Parrott and Lasky, 1998). Such effects are supported in the animal literature by the acute and subacute impact of MDMA on 5-HT, notably, delays in recovery of this transmitter in brain regions regulating emotion (Colado et al, 1999); and similar pattern reductions in other functional serotonergic factors, such as SERT and tryptophan hydroxylase (Adori et al, 2011). …”