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Updated: Jun 30, 2026
Intermittent Binge-Intake Model in Mice
Published on: January 10, 2025
S100B overexpressing mutant mice exhibit prolonged behavioural and biochemical responses towards repeated
Anna M S Kindlundh-Högberg1, Xiaoqun Zhang, Per Svenningsson
1Section of Translational Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. anna.kindlundh@fyfa.ki.se
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.
Insights
Mice overexpressing S100B showed altered responses to repeated 3,4-methylenedioxy-metamphetamine (MDMA) intake, with potentiated behaviors and less tolerance. Genetic variations in S100B may influence individual MDMA sensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- 3,4-methylenedioxy-metamphetamine (MDMA) enhances serotonin and dopamine transmission.
- Repeated MDMA binge treatment increases S100B, a neurotrophic factor, gene expression.
- S100B modulates neuronal plasticity, suggesting a role in MDMA's effects.
Purpose of the Study:
- To investigate how increased S100B expression influences MDMA-induced biochemical and behavioral responses.
- To understand the role of S100B in the development of tolerance to MDMA's effects.
- To explore genotype-dependent adaptations in neurotransmitter systems following MDMA treatment.
Main Methods:
- Utilized S100B mutant mice overexpressing the S100B gene.
- Administered repeated binge treatment with MDMA.
- Assessed behavioral responses using open-field and elevated plus-maze tests.
- Quantified serotonin transporter (SERT) and dopamine transporter densities via autoradiography.
- Measured 5-HT1B receptor density and G-protein coupling.
Main Results:
- MDMA binge treatment decreased rearing and thigmotaxis in S100B mutant mice.
- MDMA increased open-arm entries in both genotypes, but S100B mutants showed less tolerance.
- SERT density was upregulated in the substantia nigra of S100B mutant mice at baseline.
- MDMA increased SERT in wild-type mice but not in S100B mutants.
- 5-HT1B receptor density and G-protein coupling were higher in MDMA-treated S100B mutants.
Conclusions:
- Repeated MDMA treatment increases S100B mRNA expression.
- Overexpression of S100B potentiates certain exploratory and anxiolytic-like behaviors in response to MDMA.
- S100B mutant mice exhibit less tolerance to MDMA's behavioral effects.
- Genotype-dependent behavioral responses are associated with adaptations in the serotonin system.
- Genetic differences in S100B expression may contribute to individual differences in MDMA responsivity.
