Resistance of the hippocampus in the lactating rat to N-methyl-D- aspartate (NMDA)-mediated excitation is not due to a nonfunctional receptor system

The lactating rat has been shown to lack a behavioral response and immediate early gene expression (cFos) in the hippocampus (Hipc) following intravenous or intracerebroventricular administration of an N-methyl-D- aspartate (NMDA) receptor agonist. The purpose of this study is to determine whether neurons in the Hipc have an intact postsynaptic NMDA receptor system. The presence of NMDA receptor protein was determined by Western blot analysis for the NR1, NR2A, and NR2B subunits. The presence of functional NMDA receptors in the Hipc was determined by behavioral responses and the expression of cFos immunoreactivity (-ir) in response to microinjection of an NMDA receptor agonist into the hilus of the dentate gyrus. No difference in NR1 and NR2A subunit protein in the Hipc was detected between the lactating and nonlactating rats. However, there was a 26% decrease in NR2B subunit protein in this region in the lactating rat. Lactating rats receiving NMA injections displayed hyperactive behavior, similar to that observed in the nonlactating animals receiving the same treatment. The lactating rat and the nonlactating rat also displayed equivalent bilateral cFos-ir in the dentate gyms (DG), CA1 and CA3 regions of the Hipc in response to unilateral NMA injections into the Hipc. These data indicate that the lactating rat has an intact postsynaptic NMDA receptor system. Thus, Hipc refractoriness to peripheral and third ventricular injections of an NMDA receptor agonist may reflect inhibition of presynaptic input and glutamate release.