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

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Abstract

Rationale

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.

Objective

The present study dissected the discrete behavioral phases of social defeat and analyzed which behavioral characteristics may be predictive of subsequent cocaine self-administration.

Methods

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).

Results

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.

Conclusion

These data suggest that latency to enter a threatening environment is a novel behavioral characteristic predictive of later cocaine self-administration.

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Authors and Affiliations

  1. Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA

    Christopher O. Boyson, Elizabeth N. Holly, Andrew R. Burke, Sandra Montagud-Romero, Joseph F. DeBold & Klaus A. Miczek

  2. McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Elizabeth N. Holly

  3. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA

    Elizabeth N. Holly

  4. Current affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Elizabeth N. Holly

  5. Current affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    Andrew R. Burke

  6. Unidad de Investigación Psicobiología de las Drogodependencias, Departmento de Psicobiología, Universitat de València, València, Spain

    Sandra Montagud-Romero

  7. Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA

    Klaus A. Miczek

  8. Department of Pharmacology, Tufts University School of Medicine, Boston, MA, USA

    Klaus A. Miczek

  9. Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA

    Klaus A. Miczek

Authors
  1. Christopher O. Boyson
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  2. Elizabeth N. Holly
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  3. Andrew R. Burke
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  4. Sandra Montagud-Romero
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  5. Joseph F. DeBold
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  6. Klaus A. Miczek
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Corresponding author

Correspondence to Klaus A. Miczek.

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All authors declare no conflicts of interest.

Additional information

Christopher O. Boyson and Elizabeth N. Holly are co-first authors.

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Boyson, C.O., Holly, E.N., Burke, A.R. et al. Maladaptive choices by defeated rats: link between rapid approach to social threat and escalated cocaine self-administration. Psychopharmacology 233, 3173–3186 (2016). https://doi.org/10.1007/s00213-016-4363-1

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  • DOI: https://doi.org/10.1007/s00213-016-4363-1

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