Effects of N‐Methyl‐D‐Aspartate (NMDA) on Seasonal Cycles of Reproduction, Body Weight and Pelage Colour in the Male Siberian Hamster
Authors: Ebling Francis J. P. , Alexander Iona H. M. , Urbanski Henryk F. , Hastings Michael H. 
Published: September 2006

Siberian hamsters (Phodopus sungorus) transferred from stimulatory photoperiods (long days: LD) to inhibitory photoperiods (short days: SD) undergo testicular regression within 8 weeks. This reproductive response to photoperiod was blocked by systemic daily treatment with the glutamatergic agonist N‐methyl‐D‐aspartate (NMDA: 20 mg/kg BW, sc). This powerful effect of NMDA demonstrates the potential for endogenous glutamate to regulate reproductive function.

The overall aim of the subsequent studies was to investigate the site and mechanism of action of this glutamatergic agonist in order to identify potential mechanisms through which endogenous glutamate might act. To investigate whether the effect of systemic NMDA was via an effect on the circadian timing system, alterations in gonadal regression and recrudescence, seasonal coat changes (pelage) and body weight (BW) were examined. It would be predicted that long‐term cycles of all these seasonal parameters would be affected if the action of NMDA were to perturb the transduction of photoperiodic information. Daily treatments with NMDA, which initially maintained reproductive function in hamsters exposed to SD, did not influence the time course of subsequent testicular recrudescence, nor did they influence long‐term cycles of pelage and BW. Moreover, treatment with NMDA induced a dose‐dependent increase in serum concentrations of LH within 15 min of systemic injection. These data are consistent with the hypothesis that systemic NMDA exerts it reproductive effects not via an action on the circadian system, but via an action on secretion of GnRH.

To investigate potential central sites of action of glutamate, induction of the immediate early gene c‐fos, an acute marker of cellular response, was evaluated immunocytochemically (ICC) in brain areas after treatment with NMDA. Although dual‐label ICC studies revealed that NMDA did not induce c‐fos within GnRH neurons, NMDA did induce c‐fos in many cells in the region of the organum vasculosum of the lamina terminalis (OVLT), an area containing a large number of GnRH perikarya, and in the arcuate nucleus, a region close to GnRH secretory terminals in the median eminence. The lack of c‐fos induction in GnRH cells argues against a direct effect of NMDA on GnRH neurons. Thus, we examined immunocytochemically the distribution of the common NMDAR1 glutamate receptor subunit to evaluate further the potential sites of glutamatergic action. As expected, NMDAR1‐ir was widespread in perikarya throughout the brain, including the region of the OVLT and the arcuate nucleus. However, NMDAR1‐ir was also observed in cell processes in hypothalamic areas, including the median eminence, demonstrating the potential for actions of glutamate on neurosecretion in this structure. Collectively, these pharmacological, endocrine and neuroanatomical studies suggest that NMDA acts to release GnRH when delivered systemically, though not necessarily via a direct action on GnRH neurons. These findings are consistent with the view that glutamate is an important regulator of seasonal changes in reproductive function.