NMDA-mediated activation of the medial amygdala initiates a downstream neuroendocrine memory responsible for pseudopregnancy in the female rat

In female rats, genitosensory stimulation received during mating initiates twice-daily prolactin (PRL) surges, a neuroendocrine response that is the hallmark of early pregnancy or pseudopregnancy (P/PSP). Nocturnal and diurnal PRL surges are expressed repeatedly for up to 2 weeks after copulation, suggesting that a neuroendocrine memory for vaginocervical stimulation (VCS) is established at the time of mating. These studies investigated whether the processing and retention of VCS involves acute glutamatergic activation or de novo protein synthesis within the medial nucleus of the amygdala (MEA), a VCS-responsive brain site that is implicated in P/PSP initiation. Pharmacological activation of the MEA with the glutamate agonist, NMDA, initiated nocturnal PRL surges, causing a PSP state in females that had not received VCS. P/PSP initiation by mating was prevented by intra-amygdalar infusion of the NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP-5), provided that it was administered before mating. AP-5 treatment also disrupted mating-induced c-fos expression in the principle bed nucleus of the stria terminalis and the ventrolateral division of the ventromedial hypothalamic nucleus, but not in the medial or anteroventral periventricular preoptic nuclei. Neither P/PSP nor downstream cellular activation was prevented when a protein synthesis inhibitor, anisomycin, was administered to the MEA. The results indicate that MEA cells are critical to the early processing of VCS through NMDA channel activation, rapidly conveying information to downstream hypothalamic cell groups that modulate neuroendocrine function.