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 immediat e early gene expression (cFos) in the hippocampus (Hipc) following intraven ous or intracerebroventricular administration of an N-methyl-D-aspartate (N MDA) receptor agonist. The purpose of this study is to determine whether ne urons in the Hipc have an intact postsynaptic NMDA receptor system. The pre sence 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 c Fos immunoreactivity (-ir) in response to microinjection of an NMDA recepto r agonist into the hilus of the dentate gyrus. No difference in NR1 and NR2 A subunit protein in the Hipc was detected between the lactating and nonlac tating rats. However, there was a 26% decrease in NR2B subunit protein in t his region in the lactating rat. Lactating rats receiving NMA injections di splayed hyperactive behavior, similar to that observed in the nonlactating animals receiving the same treatment. The lactating rat and the nonlactatin g rat also displayed equivalent bilateral cFos-ir in the dentate gyrus (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 pos tsynaptic NMDA receptor system. Thus, Hipc refractoriness to peripheral and third ventricular injections of an NMDA receptor agonist may reflect inhib ition of presynaptic input and glutamate release. (C) 1998 Elsevier Science B.V. All rights reserved.