title: Maladaptive choices by defeated rats: link between rapid approach to social threat and escalated cocaine self-administration.
abstract: Intermittent social defeat stress engenders persistent neuroadaptations and can result in later increased cocaine taking and seeking. However, there are individual differences in stress-escalated cocaine self-administration behavior, which may be a direct result of individual differences in the manner in which rats experience social defeat stress.
  
  
  
  The present study dissected the discrete behavioral phases of social defeat and analyzed which behavioral characteristics may be predictive of subsequent cocaine self-administration.
  
  
  
  Male Long-Evans rats underwent nine intermittent social defeat episodes over 21 days in a three-compartment apparatus permitting approach to and escape from a confrontation with an aggressive resident rat. Rats then self-administered intravenous cocaine, which culminated in a 24-h unlimited access "binge." Behaviors during social defeat and cocaine self-administration were evaluated by principal component analysis (PCA).
  
  
  
  PCA revealed that the latency to enter the threatening environment was highly predictive of later cocaine self-administration during the 24-h binge. This behavior was not associated with other cocaine-predictive traits, such as reactivity to novelty in an open field, saccharin preference, and motor impulsivity. Additionally, there was no effect of latency to enter a threatening environment on physiological measures of stress, including plasma corticosterone and corticotropin releasing factor (CRF) in the extended amygdala. However, latency to enter the threatening environment was negatively correlated with brain-derived neurotropic factor (BDNF) and its receptor, tyrosine kinase B (TrkB) in the hippocampus.
  
  
  
  These data suggest that latency to enter a threatening environment is a novel behavioral characteristic predictive of later cocaine self-administration.
authors.affiliation: Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA.
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Boyson
authors.affiliation: Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA.|McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.|Current affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Holly
authors.affiliation: Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA.|Current affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Burke
authors.affiliation: Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA.|Unidad de Investigación Psicobiología de las Drogodependencias, Departmento de Psicobiología, Universitat de València, València, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Montagud-Romero
authors.affiliation: Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: DeBold
authors.affiliation: Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA. Klaus.Miczek@tufts.edu.|Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA. Klaus.Miczek@tufts.edu.|Department of Pharmacology, Tufts University School of Medicine, Boston, MA, USA. Klaus.Miczek@tufts.edu.|Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA. Klaus.Miczek@tufts.edu.
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000374:Aggression; D000818:Animals; D001522:Behavior, Animal; D002755:Choice Behavior; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D007206:Individuality; D008297:Male; D025341:Principal Component Analysis; D051381:Rats; D020318:Rats, Long-Evans; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration; D012919:Social Behavior; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology*; D013549:Sweetening Agents / Q000008:administration & dosage
chemical_list: D018765:Dopamine Uptake Inhibitors; D013549:Sweetening Agents; D003346:Corticotropin-Releasing Hormone; D012439:Saccharin; D003042:Cocaine; D003345:Corticosterone
keywords: BDNF; Behavior; Cocaine self-administration; Impulsivity; Individual differences; Social defeat stress