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This article is part of the supplement: 18th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access Meeting abstract

Neurobiological correlates of successful deep brain stimulation in a mouse model of high trait affect

Claudia Schmuckermair1, Stefano Gaburro12, Anupam Sah1, Rainer Landgraf3, Simone B Sartori1 and Nicolas Singewald1*

Author Affiliations

1 Department of Pharmacology and Toxicology, Leopold-Franzens-University of Innsbruck, 6020 Innsbruck, Austria

2 Department of Physiology, Westfälische Wilhelms-University Münster, 48149 Münster, Germany

3 Max Planck Institute of Psychiatry, 80804 Munich, Germany

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BMC Pharmacology and Toxicology 2012, 13(Suppl 1):A44  doi:10.1186/2050-6511-13-S1-A44


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/2050-6511/13/S1/A44


Published:17 September 2012

© 2012 Schmuckermair et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Recent evidence suggests that high-frequency deep brain stimulation of the nucleus accumbens (NAcb-DBS) may represent a novel therapeutic strategy for individuals suffering from treatment-resistant depression although the underlying mechanism of action remains largely unknown. Using a unique psychopathological mouse model of enhanced depression- and anxiety-like behavior (HAB) we investigated behavioral and neurobiological effects of NAcb-DBS.

Methods

HAB mice underwent either chronic treatment with different selective serotonin reuptake inhibitors (SSRIs) or stereotactic surgery to implant DBS electrodes into the NAcb. NAcb-DBS was applied for 1 h daily for seven consecutive days (130 Hz, 100 µA, 60 µs pulse width) and sham-stimulated animals were used as controls. Anxiety- and depression-related behaviors were assessed using established tests with predictive anxiolytic or antidepressant validity. Furthermore, the effects of NAcb-DBS on challenge-induced immediate early gene expression and hippocampal neurogenesis were investigated.

Results

Chronic SSRI treatment did not alter the enhanced depression-like behavior of HAB mice, while repeated, but not single, NAcb-DBS induced robust antidepressant and anxiolytic responses. Interestingly, NAcb-DBS did not affect behavior in normal depression/anxiety animals (NAB), suggesting a preferential effect of NAcb-DBS on pathophysiologically deranged systems. Antidepressant-like effects of NAcb-DBS were associated with normalization of challenge-induced dentate gyrus hypoactivity and modulation of neuronal activity in various brain regions implicated in stress and depression. Furthermore, NAcb-DBS enhanced the blunted hippocampal neurogenesis in HABs.

Conclusions

Taken together we show that the normalization of pathophysiologically enhanced depression-like behavior by repeated NAcb-DBS was associated with normalization of aberrant brain activity and rescue of impaired adult neurogenesis, indicating that DBS affects gene expression as well as neuronal plasticity in a defined, mood-associated network. Finally, it is suggested that SSRI-insensitive HAB mice represent a clinically relevant model for elucidating the neurobiological correlates underlying the observed behavioral effects of NAcb-DBS.

Acknowledgements

Supported by the Hope for Depression Research Foundation (HDRF/ISAN) and the Austrian Science Fund FWF DK SPIN (W1206).