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

作者：Wallinga Alinde E^*; de Boer Sietse F; Granneman Ramon A; Koolhaas Jaap M; Buwalda Bauke

来源：Pharmacology Biochemistry and Behavior, 2009, 94(2): 227-233.

DOI：10.1016/j.pbb.2009.08.009

• 3,4-Methylenedioxymethamphetamine
• MDMA
• Serotonin
• Dopamine
• SAL and LAL mice
• Brain
• Personality
• Coping style
• 5-HT
• DA

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.

• 出版日期2009-12