N-methyl-D-aspartic acid (NMDA) is known to stimulate adrenocorticotropin (ACTH) release after peripheral administration in spite of its inability to readily cross the blood-brain barrier (BBB). The importance of the area postrema, the hindbrain circumventricular organ which lacks a BBB, for NMDA action and ACTH release during stress was evaluated in this study. ACTH response to NMDA injection (4 mg/kg ip) was significantly reduced in rats with ablation of the area postrema compared to sham-operated animals. Integrity of the area postrema was also found to be required for full ACTH release in response to two stress stimuli (immobilization, handling). The data show that the area postrema is a brain region involved in the control of the hypothalamic-pituitary-adrenocortical (HPA) axis mediating, at least partially, the stimulatory action of NMDA and of stress stimuli on ACTH release.
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