Effects of NMDA and AMPA Receptor Antagonists on Corticosterone Facilitation of Long-term Memory in the Chick

Long-term memory formation for a weak passive avoidance task in day-old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning-related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long-term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and a-amino-3-hydroxyd-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post-training period, suggesting that their early effectiveness was not related to corticosterone-induced actions but to training-triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long-term memory-potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.