S100B overexpressing mutant mice exhibit prolonged behavioural and biochemical responses towards repeated intermittent binge treatments with MDMA.
Anna M S Kindlundh-Högberg, Xiaoqun Zhang, Per Svenningsson
The International Journal of Neuropsychopharmacology March 2009 DOI: 10.1017/s1461145708009437 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study in mice Peer reviewed |
|---|---|
| Population | Wild-type mice and mutant mice overexpressing S100B |
| Intervention | MDMA |
| Dose | 5 mg/kg, 3 times daily, 3 h apart, once per week for 4 wk |
| Duration | 4 weeks of once-weekly binge treatment |
| Measures | open-field behavior, elevated plus-maze, serotonin transporter (SERT) density, dopamine transporter density, 5-HT1B receptor density and G-protein coupling |
| Topics | MDMA |
| Key findings | Repeated MDMA treatment increased S100B mRNA. Mice overexpressing S100B showed potentiated and less tolerant exploratory and anxiolytic-like behavioral responses to MDMA, paralleled by genotype-dependent adaptations in the serotonin system. The authors propose that genetic differences in S100B expression may predispose individual differences in responsivity to repeated MDMA intake. |
Abstract
The recreational drug 3,4-methylenedioxy-metamphetamine (MDMA; 'ecstasy') enhances serotonin and dopamine transmission. Repeated binge treatment with MDMA (5 mg/kg, 3 times daily, 3 h apart, once per week for 4 wk) was found to increase gene expression of S100B, a neurotrophic factor that modulates neuronal plasticity. Mutant mice overexpressing S100B were investigated to better understand how increased S100B expression may influence MDMA-induced biochemical and behavioural responses. In open-field behaviour, the later MDMA binges decreased rearing and thigmotaxis in S100B mutant mice compared to wild-type mice. In the elevated plus-maze, MDMA increased open-arm entries in both genotypes, but less tolerance to this effect was found in S100B mutant mice. Serotonin transporter (SERT) density was up-regulated in the substantia nigra in S100B mutant mice under baseline conditions. MDMA treatment increased SERT in wild-type mice, but did not further increase it in S100B mutant mice. Dopamine transporter density was down-regulated by MDMA in both genotypes in the striatum. 5-HT1B receptor density and G-protein coupling were higher in MDMA-treated S100B mutant mice than in saline-treated mutant mice and MDMA-treated wild-type mice in the medial globus pallidus. In conclusion, repeated MDMA treatment increases S100B mRNA. Certain explorative and anxiolytic-like behaviours in response to MDMA are potentiated and exhibit less tolerance in mice overexpressing S100B. The genotype-dependent behavioural responses are paralleled by adaptations in the serotonin system. Our data indicate that genetic differences in S100B gene expression may predispose individual differences in the responsivity to repeated intake of MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 4
- Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat The Journal of Comparative Neurology March 31, 2011
- A Systematic Review of the MDMA Model to Address Social Impairment in Autism. Current Neuropharmacology 2021
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Mice in ecstasy: advanced animal models in the study of MDMA. Current Pharmaceutical Biotechnology August 1, 2010
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and 2 more in the library