Effects of N-methyl-D-aspartate receptor activation on cFos expression in luteinizing hormone-releasing hormone neurons in female rats.

Abstract

N-Methyl-D,L-aspartic acid (NMA), an agonist of N-methyl-D-aspartate (NMDA) excitatory amino acid receptors, stimulates the secretion of LH by increasing the release of LHRH. During proestrus, LHRH neurons express cFos in association with the LH surge. To determine the involvement of NMDA receptors in the activation of LHRH neurons on proestrus, we treated animals with an NMDA receptor blocker, MK-801. Treatment with MK-801 (0.3 mg/kg, sc) at 1130 h blocked both the LH and PRL surges and cFos expression in LHRH neurons. These data suggest that NMDA receptors are involved in the regulation of LHRH neuronal activation during the LH surge. We then determined whether NMA treatment could restore LH secretion and cFos expression in LHRH neurons in animals whose endogenous proestrous LH surges were blocked with pentobarbital. In the pentobarbital-blocked rats, NMA failed to induce cFos expression in LHRH neurons and increase LH secretion, but it did result in an increase in PRL secretion. To determine if NMA treatment alone could induce cFos expression in LHRH neurons, diestrous rats were treated with NMA by either systemic (40 mg/kg BW; four injections, 10 min apart) or third ventricular (2 micrograms in 2 microliters; four injections, 10 min apart) injections. NMA administration (regardless of the route of administration) caused an increase in LH secretion and significant cFos expression in many regions of the brain, including sites where the LHRH perikarya are concentrated. However, neither systemic nor intraventricular administration of NMA induced cFos expression in LHRH neurons. Thus, even though NMA results in increased activity of LHRH neurons, as evidenced by increased LH secretion, NMDA receptor activation alone appears to be insufficient to induce cFos expression in the LHRH neurons.