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  • Deep Brain Stimulation of the Nucleus Accumbens Attenuates Binge Eating in Mice: Preliminary Evidence for A Potential Therapeutic Role of Neuromodulation in Treatment-Refractory Obesity

    Final Number:

    Casey H. Halpern MD; Jeffrey G. Keating; John Wolf PhD; William C. Rodemer BS; Jurg L. Jaggi PhD; Gordon H. Baltuch MD; Marc A. Dichter Md, PhD; Tracy L. Bale PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Increasing evidence suggests that deep brain stimulation (DBS) of the nucleus accumbens (NAc) may be an effective treatment for psychiatric disorders. Dysregulation of the reward systems in the brain have been well described in many such conditions, and are presumed to underlie some component of eating disorders associated with obesity. Here, we examine whether NAc DBS can modulate the rewarding aspects of a highly palatable diet in a mouse model of binge eating.

    Methods: All mice (n=8) including non-surgical controls (n=5) were provided limited exposure to a high fat diet 1-hour daily for 7 days. During the first 4 days of this study, no stimulation was administered (DBS-off) to implanted mice (n=3). However, immediately prior to and during the 1-hour exposure on day 5 only, DBS was administered (DBS-on) unilaterally to the NAc through bipolar tungsten electrodes (40 kOhms). Biphasic symmetrical pulses were delivered at a frequency of 160 Hz and a voltage of 6 V. Binge eating was again examined on days 6 and 7 with DBS-off.

    Results: All mice exhibited binge eating after 2 days of limited exposure to the high fat diet with DBS-off. There was no significant difference in the amount of high fat food consumed on days 3 and 4 between mice with DBS-off and non-surgical controls. However, on day 5, once DBS was turned on, mice consumed significantly less of the high fat diet (0.36g ± 0.18g) compared to controls (0.87g ± 0.05g) (p<0.01). Binge eating returned on days 6 and 7 with DBS-off. See Figure 1.

    Conclusions: DBS of the NAc significantly attenuated binge eating in mice compared to non-surgical controls in this preliminary experiment, providing impetus for additional studies with larger sample sizes, within-group comparisons, alternative stimulatory parameters, and control for anatomic specificity.

    Patient Care: This project serves as preliminary translational work where further studies will need to be pursued before attempting deep brain stimulation in larger animal models of obesity. It may be that if deep brain stimulation appears safe and effective, it may be a reasonable adjunct to current treatment protocols for obesity.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of investigating deep brain stimulation in animal models of eating disorders 2) Discuss, in small groups the possible therapeutic role for deep brain stimulation in obesity 3) Identify an effective treatment for eating disorders associated with treatment refractory obesity that needs to be studied in greater detail in animal models

    References: Halpern CH, Wolf JA, Bale TL, Stunkard AJ, Danish SF, Grossman M, Jaggi JL, Grady MS, Baltuch GH.Deep brain stimulation in the treatment of obesity. J Neurosurg. 2008 Oct;109(4):625-34. Pisapia JM, Halpern CH, Williams NN, Wadden TA, Baltuch GH, Stein SC. Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study. Neurosurg Focus. 2010 Aug;29(2):E15 Pankevich DE, Teegarden SL, Hedin AD, Jensen CL, Bale TL. Caloric restriction experience reprograms stress and orexigenic pathways and promotes binge eating. J Neurosci. 2010 Dec 1;30(48):16399-407. Teegarden SL, Bale TL. Effects of stress on dietary preference and intake are dependent on access and stress sensitivity. Physiol Behav. 2008 Mar 18;93(4-5):713-23. Vassoler FM, Schmidt HD, Gerard ME, Famous KR, Ciraulo DA, Kornetsky C, Knapp CM, Pierce RC. Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats. J Neurosci. 2008 Aug 27;28(35):8735-9.

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