Long-term neurobiological consequences of ecstasy: A role for pre-existing trait-like differences in brain monoaminergic functioning?

Alinde E. Wallinga*, Sietse F. de Boer, Ramon A. Granneman, Jaap M. Koolhaas, Bauke Buwalda

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

This study investigated whether trait-like differences in brain monoaminergic functioning relate to differential vulnerability for the long-term neurochemical depletion effects of MDMA. Genetically selected aggressive (SAL) and non-aggressive (LAL) house-mice differing in baseline serotonergic and dopaminergic neurotransmission were administered MDMA. An acute binge-like MDMA injection protocol (three times, using either of the dosages of 0, 5, 10 and 20 mg/kg i.p. with 3 h interval) was employed. Three and 28 days after treatment with MDMA induced a dose-dependent depletion of striatal dopamine and its metabolites that did not differ between SAL and LAL mice. Similarly, the dose-dependent MDMA-induced serotonergic depletion did not differ between lines 3 days after treatment. Interestingly, 28 days after MDMA in LAL mice, 5-HT and 5-HIAA levels were still significantly depleted after treatment with 3 x 10 mg/kg, while in SAL mice 5-HT depletion was only seen after the highest dosage. Surprisingly. LAL mice did not show any long-term 5-HT depletion after treatment with the highest dose. In conclusion, only LAL mice are able to restore initial severe loss of MDMA-evoked 5-HT and 5-HIAA levels. SAL and LAL mice are differentially susceptible for the long-term but not short-term MDMA-induced serotonergic depletion in the striatum. The differentiation between both lines in the long-term striatal serotonergic response to MDMA seems to depend on the capacity of the brain to adapt to the short-term depletion of monoaminergic levels and may somehow be related to individual, trait-like characteristics of brain monoaminergic systems. (C) 2009 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Volume94
Issue number2
DOIs
Publication statusPublished - Dec-2009

Keywords

  • 3,4-Methylenedioxymethamphetamine
  • MDMA
  • Serotonin
  • Dopamine
  • SAL and LAL mice
  • Brain
  • Personality
  • Coping style
  • 5-HT
  • DA
  • WILD HOUSE MICE
  • RAT-BRAIN
  • 5-HT1A RECEPTOR
  • MDMA ECSTASY
  • 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA
  • METHYLENEDIOXYMETHAMPHETAMINE MDMA
  • SUBSTITUTED AMPHETAMINES
  • NONAGGRESSIVE MICE
  • TRANSGENIC MICE
  • SYSTEM FUNCTION

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