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Brain monoamines and antidepressant-like responses in MRL/MpJ versus C57BL/6J mice
Darrick T Balu1, Jill R Turner, Bethany R Brookshire
1Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
The MRL/MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments. This study compared brain monoamine systems between MRL/MpJ and C57BL/6J mice as a potential basis for strain differences after chronic antidepressant treatment. MRL/MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions. Microdialysis studies demonstrated that baseline levels of extracellular serotonin did not differ between strains. However, acute administration of the selective serotonin reuptake inhibitor citalopram produced an increase in extracellular serotonin in the ventral hippocampus of MRL/MpJ mice that was twice as large as achieved in C57BL/6J mice. The greater effects in MRL/MpJ mice on 5-HT levels were not maintained after local perfusion of citalopram, suggesting that mechanisms outside of the hippocampus were responsible for the greater effect of citalopram after systemic injection. The density of serotonin and norepinephrine transporters in the hippocampus was significantly higher in MRL/MpJ mice. In addition, the expression of 5-HT(1A) mRNA was lower in the hippocampus, 5-HT(1B) mRNA was higher in the hippocampus and brainstem and SERT mRNA was higher in the brain stem of MRL/MpJ mice. The exaggerated neurotransmitter release in MRL/MpJ mice was accompanied by reduced baseline immobility in the tail suspension test and a greater reduction of immobility produced by citalopram or the tricyclic antidepressant desipramine. These data suggest that differences in the response to acute and chronic antidepressant treatments between the two strains could be attributed to differences in serotonin or catecholamine transmission.
Insights
MRL/MpJ mice show enhanced antidepressant responses due to differences in serotonin and dopamine transmission compared to C57BL/6J mice. These brain variations may explain their improved healing and regeneration.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- MRL/MpJ mice exhibit superior wound healing and tissue regeneration.
- This strain also shows increased neurotrophic responses to chronic antidepressant treatments.
- Investigating neurochemical differences may explain these strain-specific responses.
Purpose of the Study:
- To compare brain monoamine systems between MRL/MpJ and C57BL/6J mice.
- To identify potential neurobiological underpinnings for differential responses to antidepressant drugs.
- To explore strain differences in serotonin and dopamine transmission.
Main Methods:
- Tissue monoamine level analysis.
- In vivo microdialysis to measure extracellular serotonin.
- Assessment of antidepressant effects using the tail suspension test.
- Quantification of transporter density and mRNA expression for serotonin and norepinephrine transporters.
Main Results:
- MRL/MpJ mice had higher brain serotonin and dopamine levels.
- Citalopram induced a greater increase in extracellular serotonin in MRL/MpJ mice's hippocampus.
- Higher densities of serotonin and norepinephrine transporters were observed in MRL/MpJ mice.
- MRL/MpJ mice showed reduced immobility in the tail suspension test, with greater antidepressant-induced reduction.
Conclusions:
- Differences in serotonin and catecholamine transmission contribute to the distinct responses of MRL/MpJ and C57BL/6J mice to antidepressants.
- Enhanced monoamine system function in MRL/MpJ mice may underlie their regenerative capabilities and antidepressant efficacy.
- Strain-specific neurochemical profiles are critical for understanding variable drug responses and physiological functions.
