title: Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm.
abstract: Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors).
  
  
  
  We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity.
  
  
  
  After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies.
  
  
  
  Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress.
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea. Electronic address: Seojh@yuhs.ac.
authors.forename: Jeho
authors.initials: J
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea. Electronic address: HOJINCHO@yuhs.ac.
authors.forename: Hojin
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea. Electronic address: MOON@yuhs.ac.
authors.forename: Gun Tae
authors.initials: GT
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, South Korea. Electronic address: kimhoon@yuhs.ac.
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea. Electronic address: dgkimpahrm@yuhs.ac.
authors.forename: Dong Goo
authors.initials: DG
authors.lastname: Kim
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000378:metabolism / Q000503:physiopathology*; D005973:Glutamine / Q000378:metabolism; D006380:Helplessness, Learned; D051381:Rats; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D005973:Glutamine
keywords: Coping strategy; Learned helplessness; Major depressive disorder; Resting brain activity; Stress