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Social defeat stress, sensitization, and intravenous cocaine self-administration in mice

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Abstract

Rationale

Behavioral sensitization has been proposed as a process that is important in compulsive drug use and in psychotic disorders.

Objective

The present experiments examine the relationship between behavioral sensitization, induced by either social defeat or amphetamine, and intravenous cocaine self-administration in mice.

Materials and methods

Male CFW mice were exposed either to defeat experiences, amphetamine (2.5 mg/kg, i.p.) or saline (i.p.) every day for 10 days. Ten days after the last defeat or injection, mice were challenged with varying doses of amphetamine (1.0–2.5 mg/kg i.p). Mice were then trained to nose poke for intravenous cocaine (1.0 mg/kg/inf) during daily 3-h sessions. Following this acquisition phase, the animals self-administered varying doses of cocaine (0.3–1.8 mg/kg/inf) or were allowed to self-administer cocaine (0.3 mg/kg/inf) according to a progressive ratio schedule of reinforcement.

Results

Repeated social defeat produced a sensitized motor response to a single challenge of 1.5 mg/kg amphetamine and to a cumulative dosing of amphetamine. Amphetamine-pretreated mice exhibited increased cocaine self-administration during acquisition and elevated break points during performance on a progressive ratio schedule of reinforcement relative to stress-sensitized and control animals.

Conclusions

These data extend the evidence from rats to mice for the process of sensitization leading to more cocaine taking. Contrary to what is seen in rats, increased levels of cocaine self-administration were seen only in the amphetamine-pretreated mice and not after repeated defeat stress, suggesting that the sensitized response to defeat stress may not be as robust as it is in rats in this particular strain of mice.

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Acknowledgements

This work was supported by grants from the National Institute on Drug Abuse (DA02623 and DA018478). The authors wish to thank Gwen Campbell, Andrea Fydl, and Lauren Friedman for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Psychology, Tufts University, 490 Boston Ave., Medford, MA, 02155, USA

    Jasmine J. Yap & Klaus A. Miczek

  2. Department of Psychiatry, Tufts University, Boston, MA, 02111, USA

    Klaus A. Miczek

  3. Department of Pharmacology, Tufts University, Boston, MA, 02111, USA

    Klaus A. Miczek

  4. Department of Neuroscience, Tufts University, Boston, MA, 02111, USA

    Klaus A. Miczek

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Correspondence to Jasmine J. Yap.

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Yap, J.J., Miczek, K.A. Social defeat stress, sensitization, and intravenous cocaine self-administration in mice. Psychopharmacology 192, 261–273 (2007). https://doi.org/10.1007/s00213-007-0712-4

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