Nucleus Accumbens Deep Brain Stimulation Suppresses Binge Eating in Mice: a Mechanistic Approach

Casey Harrison Halpern, MD1, Jeffrey Keating, PhD1, John Wolf, PhD1, Mark Attiah, BS1, Jurg Jaggi, PhD1, Gordon Baltuch, MD, PhD1, Marc Dichter, MD1, Tracy Bale, PhD1

1Philadelphia, PA United States

Keywords: behavior, deep brain stimulation, eating disorder, animal model, mechanism

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     The nucleus accumbens (NAc) shell has been implicated in eating disorders associated with obesity.
     Here, we test the hypothesis that deep brain stimulation (DBS) of the NAc-shell would attenuate binge eating in mice. We measured c-Fos protein levels to assay neuronal activation in response to DBS.
     Mice (C57Bl/6) were implanted unilaterally in the NAc-shell (confirmed post-mortem) with a bipolar electrode. Implanted mice (n=12) and non-surgical controls (n=7) were provided 1h, daily exposure to a high fat diet for 7 days. We defined binge eating as consumption of 25% of daily caloric intake. Immediately prior to and during exposure to this diet on days 8 and 10, DBS was administered (DBS-on; 160 Hz, 60 ms, 150 mA). Binge eating was re-examined on days 9 and 11 with DBS-off. We then measured c-Fos protein in the NAc-shell immediately following DBS and binge eating in controls.
     Stable levels of binge eating were seen. DBS was then administered, which significantly suppressed binge eating compared to controls (p<0.05) and within-group on DBS-off days (p<0.01). C-Fos increased specifically in the NAc-shell in response to DBS both ipsilateral and contralateral to the electrode. There was a modest increase in c-Fos in the NAc-shell bilaterally following binge eating in controls.
     This is a mouse study.
     NAc-shell DBS significantly attenuated binge eating and may be related to increased neuronal activation in the shell in response to DBS. C-Fos levels increased bilaterally following unilateral DBS.
     This is the first report to our knowledge to identify bilateral accumulation of c-Fos in response to unilateral DBS.


Project Roles:

C. Halpern (), J. Keating (), J. Wolf (), M. Attiah (), J. Jaggi (), G. Baltuch (), M. Dichter (), T. Bale ()