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Behavioral sensitization due to social defeat stress in mice: antagonism at mGluR5 and NMDA receptors

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Abstract

Rationale

Repeated administration of psychostimulants progressively augments the behavioral response to and increases self-administration behavior of these drugs. Experience of repeated intermittent social defeat stress episodes also leads to a sensitized locomotor response following psychostimulant challenge. Both metabotropic and ionotropic glutamate receptors have been shown to be critical in the induction and expression of stimulant sensitization, but their role in sensitization due to social defeat stress remains unclear.

Objective

We evaluated the role of mGluR5 and NMDA glutamate receptors in the development of amphetamine-induced and social defeat stress-induced sensitization, using the non-competitive mGluR5 antagonist, MPEP, and the non-competitive NMDA antagonist, dizocilpine (MK-801).

Methods

In adult, male CFW mice, sensitization was induced by either ten daily injections of d-amphetamine (1 mg/kg) or ten daily brief episodes of social defeat. Mice were pretreated with MPEP (3 mg/kg or 10 mg/kg) or dizocilpine (0.1 mg/kg) prior to amphetamine injections. Mice subjected to social defeat were pretreated with MPEP (10 mg/kg) or dizocilpine (0.1 mg/kg). Ten days after induction, the expression of locomotor sensitization to amphetamine was determined.

Results

The induction of sensitization due to social defeat stress was prevented by MPEP, yet MPEP did not inhibit the development of behavioral sensitization to amphetamine. Confirming and extending earlier results, dizocilpine pretreatment blocked both amphetamine-induced and stress-induced sensitization.

Conclusions

These data indicate that behavioral sensitization to social defeat stress is dependent on mGluR5 receptors, whereas low-dose amphetamine sensitization may not be.

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Acknowledgements

This research was supported by USPHS research grant DA02632.

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Authors and Affiliations

  1. Department of Psychology, Tufts University, Medford, Mass., USA

    Jasmine J. Yap, Herbert E. Covington III, Melissa C. Gale, Rupak Datta & Klaus A. Miczek

  2. Department of Psychiatry, Tufts University, Boston, Mass., USA

    Klaus A. Miczek

  3. Department of Pharmacology, Tufts University, Boston, Mass., USA

    Klaus A. Miczek

  4. Department of Neuroscience, Tufts University, 530 Boston Avenue (Bacon Hall), Medford, MA, 02155, USA

    Klaus A. Miczek

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  1. Jasmine J. Yap
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  2. Herbert E. Covington III
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  5. Klaus A. Miczek
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Correspondence to Klaus A. Miczek.

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Yap, J.J., Covington, H.E., Gale, M.C. et al. Behavioral sensitization due to social defeat stress in mice: antagonism at mGluR5 and NMDA receptors. Psychopharmacology 179, 230–239 (2005). https://doi.org/10.1007/s00213-004-2023-3

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