Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in Dark Agouti rat

J Comp Neurol. 2011 Aug 15;519(12):2353-78. doi: 10.1002/cne.22631.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aging / drug effects*
  • Animals
  • Body Temperature
  • Body Weight
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Humans
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology
  • Nerve Fibers / drug effects*
  • Nerve Fibers / metabolism
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism*
  • Serotonin Agents / administration & dosage*
  • Serotonin Agents / pharmacology
  • Young Adult


  • Brain-Derived Neurotrophic Factor
  • Serotonin Agents
  • Serotonin
  • N-Methyl-3,4-methylenedioxyamphetamine