Citation

Wallinga AE, de Boer SF, Granneman RA, Koolhaas JM, Buwalda B. Pharmacol. Biochem. Behav. 2009; 94(2): 227-233.

Affiliation

Department of Behavioral Physiology, Biological Centre, University of Groningen, Haren, The Netherlands. A.E.Wallinga@rug.nl

Copyright

(Copyright © 2009, Elsevier Publishing)

DOI

10.1016/j.pbb.2009.08.009

PMID

19699758

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 20mg/kg i.p. with 3h 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 3x10 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.

Language: en