title: Long-term neurobiological consequences of ecstasy: a role for pre-existing trait-like differences in brain monoaminergic functioning?
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.
authors.affiliation: Department of Behavioral Physiology, Biological Centre, University of Groningen, Haren, The Netherlands. A.E.Wallinga@rug.nl
authors.forename: Alinde E
authors.initials: AE
authors.lastname: Wallinga
authors.forename: Sietse F
authors.initials: SF
authors.lastname: de Boer
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Granneman
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Koolhaas
authors.forename: Bauke
authors.initials: B
authors.lastname: Buwalda
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012701:Serotonin / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D015306:Biogenic Monoamines; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine