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The glutamate agonist NMDA blocks gonadal regression and enhances antibody response to an immune challenge in Siberian hamsters (Phodopus sungorus)

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Abstract

Seasonal variation in behavior and physiology, including changes in immune function, are common. This variability is elicited by changes in photoperiod and often covaries with fluctuations in both energy reserves and reproductive state. It is unclear, however, whether changes in either variable alone drive seasonal changes in immunity. We investigated the relative contributions of reproduction and energy balance to changes in immune function. To accomplish this, we uncoupled seasonal changes in reproduction from those related to energy balance via daily injections of N-methyl-d-aspartate (NMDA) in Siberian hamsters (Phodopus sungorus). NMDA is a glutamatergic agonist that blocks short day-induced gonadal regression, while leaving short-day declines in body mass unaffected. In Experiment 1, we examined the effect of differing doses of NMDA on testosterone production as a proxy for NMDA effects on reproduction; a dose-dependent rise in testosterone was observed. In Experiment 2, animals were maintained on long or short days and received daily injections of NMDA. After 8 weeks, all animals underwent a humoral immune challenge. Short-day animals receiving daily injections of NMDA maintained long day-like gonads; however, contrary to our predictions, no trade-off between reproduction or energy balance and immune function was observed. Unexpectedly, NMDA treatment increased immunoglobulin levels in all groups, suggesting that NMDA may provide an immunomodulatory signal, presumably through actions on peripheral glutamate receptors. These results support a previous finding that NMDA blocks reproductive regression. In addition, these findings demonstrate a general immunoenhancing effect of NMDA that appears independent of changes in reproductive or energetic state of the animal.

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Acknowledgments

We would like to thank Lisa Garatoni, Laura Garman, Jill Lodde and Trevor Brown for expert animal assistance. This work was supported by an SICB Grant-in-Aid (T.J.G.), an NIH/T32 training grant HD049336-0 (T.J.G., S.S.F), an Eli Lilly METACyt grant, Indiana University Faculty Research Support Program and NSF IOB:0543798 (G.E.D).

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  1. Timothy J. Greives

    Present address: Timothy Greives, Max Planck Institute for Ornithology, Vogelwarte Radolfzell, Schlossallee 1b, 78315, Radolfzell, Germany

Authors and Affiliations

  1. Department of Biology, Center for the Integrative Study of Animal Behavior and Program in Neuroscience, Indiana University, 1001 E. 3rd St., Bloomington, IN, 47405-3700, USA

    Timothy J. Greives, Devin A. Zysling, Nicholas W. Garcia & Gregory E. Demas

  2. Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT, 84322, USA

    Susannah S. French

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  1. Timothy J. Greives
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Correspondence to Timothy J. Greives.

Additional information

Communicated by G. Heldmaier.

The authors T. J. Greives and S. S. French contributed equally to this work.

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Greives, T.J., French, S.S., Zysling, D.A. et al. The glutamate agonist NMDA blocks gonadal regression and enhances antibody response to an immune challenge in Siberian hamsters (Phodopus sungorus). J Comp Physiol B 180, 267–277 (2010). https://doi.org/10.1007/s00360-009-0411-z

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  • DOI: https://doi.org/10.1007/s00360-009-0411-z

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