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 h allmark of early pregnancy or pseudopregnancy (P/PSP). Nocturnal and diurna l PRL surges are expressed repeatedly for up to 2 weeks after copulation, s uggesting that a neuroendocrine memory for vaginocervical stimulation (VCS) is established at the time of mating. These studies investigated whether t he 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. Phar macological activation of the MEA with the glutamate agonist, NMDA, initiat ed nocturnal PRL surges, causing a PSP state in females that had not receiv ed VCS. P/PSP initiation by mating was prevented by intra-amygdalar infusio n of the NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP-5) , provided that it was administered before mating. AP-5 treatment also disr upted mating-induced c-fos expression in the principle bed nucleus of the s tria terminalis and the ventrolateral division of the ventromedial hypothal amic nucleus, but not in the medial or anteroventral periventricular preopt ic nuclei. Neither P/PSP nor downstream cellular activation was prevented w hen a protein synthesis inhibitor, anisomycin, was administered to the MEA. The results indicate that MEA cells are critical to the early processing o f VCS through NMDA channel activation, rapidly conveying information to dow nstream hypothalamic cell groups that modulate neuroendocrine function.