title: Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation.
abstract: Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive-compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, whereas the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice and was found to acutely reduce caloric intake and induce weight loss. Together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system.
authors.affiliation: Departments of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Casey H
authors.initials: CH
authors.lastname: Halpern
authors.forename: Anand
authors.initials: A
authors.lastname: Tekriwal
authors.forename: Jessica
authors.initials: J
authors.lastname: Santollo
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Keating
authors.forename: John A
authors.initials: JA
authors.lastname: Wolf
authors.forename: Derek
authors.initials: D
authors.lastname: Daniels
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Bale
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002032:Bulimia / Q000503:physiopathology* / Q000628:therapy*; D046690:Deep Brain Stimulation / Q000379:methods*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000502:physiology*; D011897:Random Allocation; D017448:Receptors, Dopamine D2 / Q000502:physiology*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; C534628:SCH 23390