title: Cellular adaptations of dorsal raphe serotonin neurons associated with the development of active coping in response to social stress.
abstract: BACKGROUND
  Social stress is a risk factor for affective disorders for certain vulnerable individuals. Stress and depression are linked in part through regulation of the dorsal raphe (DR)-serotonin (5-HT) system by the stress-related neuropeptide, corticotropin-releasing factor (CRF). We used a rat social stress model that shows individual differences in coping strategies to determine whether differences in CRF-5-HT interactions underlie individual differences in the vulnerability to social stress.
  
  
  METHODS
  Rats were exposed to the resident-intruder model of social stress for 5 days. In vivo single-unit recordings assessed DR-5-HT neuronal responses to CRF and immunoelectron microscopy assessed CRF1 and CRF2 cellular localization 24 hours after the last stress.
  
  
  RESULTS
  Rats responded to social stress passively, assuming defeat with short latencies (48%), or actively, with proactive behaviors and longer defeat latencies (LL, 52%). Whereas CRF (30 ng, intra-DR) inhibited 5-HT neuronal activity of control and SL rats, it activated 5-HT neurons of LL rats, an effect that was CRF2-mediated. Consistent with this, social stress promoted CRF1 internalization together with CRF2 recruitment to the plasma membrane of DR neurons selectively in LL rats.
  
  
  CONCLUSIONS
  These data suggest that a proactive coping strategy toward social stress is associated with a redistribution of CRF1 and CRF2 in DR-5-HT neurons that primes the system to be activated by subsequent stress. The lack of this adaptation in passive coping rats may contribute to their depressive-like phenotype. These studies provide a cellular mechanism for individual differences in stress responses and consequences.
authors: Department of Anesthesia and Critical Care Medicine, Division of Stress Neurobiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. susan.wood@uscmed.sc.edu
authors: Susan K
authors: SK
authors: Wood
authors: Xiao-Yan
authors: XY
authors: Zhang
authors: Beverly A S
authors: BA
authors: Reyes
authors: Catherine S
authors: CS
authors: Lee
authors: Elisabeth J
authors: EJ
authors: Van Bockstaele
authors: Rita J
authors: RJ
authors: Valentino
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000220:Adaptation, Biological / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004195:Disease Models, Animal; D007206:Individuality; D008297:Male; D016253:Microscopy, Immunoelectron; D010446:Peptide Fragments / Q000494:pharmacology; D011903:Raphe Nuclei / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism / Q000648:ultrastructure; D059326:Serotonergic Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000473:pathology* / Q000523:psychology*; D000071557:beta-Arrestins; D000099052:CRF Receptor, Type 1
chemical_list: D019390:Arrestins; C101531:CRF receptor type 2; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C116607:antisauvagine 30; D000071557:beta-Arrestins; C070614:neurobiotin; D012701:Serotonin; D000099052:CRF Receptor, Type 1; D001710:Biotin; D003346:Corticotropin-Releasing Hormone