title: Neurogenesis and helplessness are mediated by controllability in males but not in females.
abstract: BACKGROUND
  Numerous studies have implicated neurogenesis in the hippocampus in animal models of depression, especially those related to controllability and learned helplessness. Here, we tested the hypothesis that uncontrollable but not controllable stress would reduce cell proliferation in the hippocampus of male and female rats and would relate to the expression of helplessness behavior.
  
  
  METHODS
  To manipulate controllability, groups of male and female rats were trained in one session (acute stress) or over seven sessions (repeated stress) to escape a footshock, whereas yoked control subjects could not escape but were exposed to the same amount of stress. Cell proliferation was assessed with immunohistochemistry of bromodeoxyuridine (BrdU) and immunofluorescence of BrdU and neuronal nuclei (NeuN). Separate groups were exposed to either controllable or uncontrollable stress, and their ability to learn to escape during training on a more difficult task was used as a behavioral measure of helplessness.
  
  
  RESULTS
  Acute stress reduced cell proliferation in males but did not affect proliferation in the female hippocampus. When animals were given the opportunity to learn to control the stress over seven days, males produced more cells than the yoked males without control. Repeated training with controllable stress did not influence proliferation in females. Under all conditions, males were more likely than females to express helplessness behavior, even males that were not previously stressed.
  
  
  CONCLUSIONS
  The modulation of neurogenesis by controllability was evident in males but not in females, as was the expression of helplessness behavior, despite the fact that men are less likely than women to experience depression.
authors.affiliation: Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA. shors@rutgers.edu
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Shors
authors.forename: Jason
authors.initials: J
authors.lastname: Mathew
authors.forename: Helene M
authors.initials: HM
authors.lastname: Sisti
authors.forename: Carol
authors.initials: C
authors.lastname: Edgecomb
authors.forename: Steven
authors.initials: S
authors.lastname: Beckoff
authors.forename: Christina
authors.initials: C
authors.lastname: Dalla
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D003863:Depression / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006380:Helplessness, Learned; D006624:Hippocampus / Q000473:pathology; D008297:Male; D009474:Neurons / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology
chemical_list: D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine