AMPA receptors in the medial amygdala are critical for establishing a neuroendocrine memory in the female rat

Abstract

We sought to examine AMPA receptor (AMPAR) function in the medial posterodorsal amygdala (MePD), as glutamate neurotransmission is critical for the neural response to vaginal-cervical stimulation that initiates pregnancy or pseudopregnancy. Female rats were infused with the AMPAR antagonist CNQX or vehicle directly into the MePD via bilaterally implanted cannulae, then either returned to their homecage (HC), or received 15 mounts-without-intromissions (MO) or 15 intromissions (15I) from a male. Expression of the activity marker EGR-1 was used to determine the CNQX concentration which would prevent mating-induced activation of MePD neurons. Separate cannulated females received CNQX infusions into the MePD prior to receiving 15I, and the oestrous cycle length was monitored by daily vaginal lavages. Infusion of CNQX (500 nm) blocked mating-induced neural activation and lengthened the oestrous cycle, demonstrating AMPAR involvement in the formation of pseudopregnancy. To further explore this involvement, separate groups of 15I, MO and HC females were killed 90 min or 3 h after testing treatment. Brain sections were immunolabeled for AMPAR-subunit GluR1 phosphorylated at one of two sites (Serine-831 or Serine-845), or total GluR1 and GluR2, and immunofluorescence intensity was measured in the MePD, hippocampus and hypothalamus. A mating-induced increase in Serine-831 phosphorylation after 3 h was observed only in the MePD, whereas there was no effect on Serine-845 phosphorylation. Additionally, we observed a time-dependent increase in total GluR1 staining intensity. These results suggest an increased AMPAR function in the MePD after receipt of VCS, and a role for AMPAR in the neural response to VCS resulting in pseudopregnancy.