, Volume 232, Issue 6, pp 991–1001 | Cite as

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone

  • Kevin J. Norman
  • Jacob A. Seiden
  • Jacob A. Klickstein
  • Xiao Han
  • Lara S. Hwa
  • Joseph F. DeBold
  • Klaus A. MiczekEmail author
Original Investigation



Stress experiences have been shown to be a risk factor for alcohol abuse in humans; however, a reliable mouse model using episodic social stress has yet to be developed.


The current studies investigated the effects of mild and moderate social defeat protocols on plasma corticosterone, voluntary alcohol drinking, and motivation to drink alcohol.


Outbred Carworth Farms Webster (CFW) mice were socially defeated for 10 days during which the intruder mouse underwent mild (15 bites: mean = 1.5 min) or moderate (30 bites: mean = 3.8 min) stress. Plasma corticosterone was measured on days 1 and 10 of the defeat. Ethanol drinking during continuous access to alcohol was measured 10 days following the defeat or 10 days prior to, during, and 20 days after the defeat. Motivation to drink was determined using a progressive ratio (PR) operant conditioning schedule during intermittent access to alcohol.


Plasma corticosterone was elevated in both stress groups on days 1 and 10. Ethanol consumption and preference following moderate stress were higher (13.3 g/kg/day intake) than both the mild stress group (8.0 g/kg/day) and controls (7.4 g/kg/day). Mice with previously acquired ethanol drinking showed decreased alcohol consumption during the moderate stress followed by an increase 20 days post-defeat. Moderately stressed mice also showed escalated ethanol intake and self-administration during a schedule of intermittent access to alcohol.


Social defeat experiences of moderate intensity and duration led to increased ethanol drinking and preference in CFW mice. Ongoing work investigates the interaction between glucocorticoids and dopaminergic systems as neural mechanisms for stress-escalated alcohol consumption.


Stress Social defeat Drug abuse Corticosterone Mice Self-administration Animal models Ethanol 



This research was supported by NIH grants AA013983 and DA031734 (Klaus Miczek, Ph.D.) and F31 AA021622 (Lara Hwa). The authors would like to thank Tom Sopko and Peter Andrew for their outstanding contributions.

Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Kevin J. Norman
    • 1
  • Jacob A. Seiden
    • 1
  • Jacob A. Klickstein
    • 1
  • Xiao Han
    • 1
  • Lara S. Hwa
    • 1
  • Joseph F. DeBold
    • 1
  • Klaus A. Miczek
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of PsychologyTufts UniversityMedfordUSA
  2. 2.Department of NeuroscienceTufts UniversityBostonUSA
  3. 3.Department of PharmacologyTufts UniversityBostonUSA
  4. 4.Department of PsychiatryTufts UniversityBostonUSA
  5. 5.Tufts UniversityMedfordUSA

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