, Volume 233, Issue 17, pp 3173–3186 | Cite as

Maladaptive choices by defeated rats: link between rapid approach to social threat and escalated cocaine self-administration

  • Christopher O. Boyson
  • Elizabeth N. Holly
  • Andrew R. Burke
  • Sandra Montagud-Romero
  • Joseph F. DeBold
  • Klaus A. MiczekEmail author
Original Investigation



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.


Social defeat stress Cocaine self-administration BDNF Impulsivity Behavior Individual differences 


Compliance with ethical standards

Conflicts of interest

All authors declare no conflicts of interest.

Supplementary material

213_2016_4363_MOESM1_ESM.docx (134 kb)
ESM 1 (DOCX 133 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Christopher O. Boyson
    • 1
  • Elizabeth N. Holly
    • 1
    • 2
    • 3
    • 4
  • Andrew R. Burke
    • 1
    • 5
  • Sandra Montagud-Romero
    • 1
    • 6
  • Joseph F. DeBold
    • 1
  • Klaus A. Miczek
    • 1
    • 7
    • 8
    • 9
    Email author
  1. 1.Department of PsychologyTufts UniversityMedfordUSA
  2. 2.McGovern Institute for Brain ResearchMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of Brain and Cognitive SciencesMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Current affiliation: Department of Neuroscience, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Current affiliation: Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  6. 6.Unidad de Investigación Psicobiología de las Drogodependencias, Departmento de PsicobiologíaUniversitat de ValènciaValènciaSpain
  7. 7.Department of PsychiatryTufts University School of MedicineBostonUSA
  8. 8.Department of PharmacologyTufts University School of MedicineBostonUSA
  9. 9.Department of NeuroscienceTufts University School of MedicineBostonUSA

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