title: Sex differences in behavioral and neural cross-sensitization and escalated cocaine taking as a result of episodic social defeat stress in rats.
abstract: BACKGROUND
  Episodic social defeat stress results in cross-sensitization to cocaine, characterized by augmentation of locomotor activity, dopamine (DA) levels in the nucleus accumbens (NAc), and cocaine self-administration during a 24-h "binge" in male rats. However, females are more vulnerable than males at each phase of cocaine addiction, and while these sex differences have been replicated in rats, the role of social stress in females remains largely neglected.
  
  
  OBJECTIVE
  This study examined sex and estrous cycle differences in behavioral and dopaminergic cross-sensitization to cocaine, as well as cocaine taking in an unlimited-access self-administration "binge."
  
  
  METHODS
  Long-Evans rats underwent episodic social defeat and were assessed 10 days later for either (1) behavioral sensitization, as determined by locomotor activity in response to acute cocaine (10 mg/kg, i.p.), (2) neural sensitization, as determined by in vivo microdialysis of DA in the NAc shell in response to acute cocaine, or (3) intravenous self-administration of cocaine (0.3 mg/kg/infusion) in an unlimited-access "binge."
  
  
  RESULTS
  Social defeat stress resulted in behavioral and dopaminergic cross-sensitization in both sexes, but the effect was larger and longer lasting in stressed females. Furthermore, while stress engendered a longer "binge" in both sexes, females had a significantly longer "binge" duration than males.
  
  
  CONCLUSIONS
  These data suggest that socially stressed females exhibit a larger and longer lasting behavioral and neural cross-sensitization, as well as more dysregulated cocaine taking, than males possibly due to different alterations in the dopaminergic response in the NAc. Furthermore, estrogens appear to play a facilitatory role in both behavioral and dopaminergic sensitization.
authors.affiliation: Department of Psychology, Tufts University, 530 Boston Avenue, Medford, MA 02155, USA. elizabeth.holly@tufts.edu
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Holly
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimamoto
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Debold
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D004291:Dominance-Subordination; D004298:Dopamine / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D012737:Sex Factors; D012919:Social Behavior; D013315:Stress, Psychological / Q000523:psychology*; D013997:Time Factors
chemical_list: D004967:Estrogens; D003042:Cocaine; D004298:Dopamine