Effect of central administration of the non-NMDA receptor antagonist DNQX on ACTH and corticosterone release before and during immobilization stress.

The purpose of the present study was to evaluate the role of central alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate type of glutamate receptors in the control of ACTH and corticosterone release under basal and stress conditions. AMPA/ kainate competitive receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX), which does not penetrate the blood-brain barrier, was administered intracerebroventricularly (i.c.v.). A modified method for i.c.v. drug administration in conscious freely moving rats was employed. DNQX or artificial cerebrospinal fluid (aCSF) was injected into lateral ventricle through a thin polyethylene cannula with a steel needle on the end which was inserted and moved via large polyethylene cannula to the guide stainless steel cannula. This procedure was performed out of the cage. ACTH and corticosterone release under basal conditions and during immobilization stress were investigated. Intracerebroventricular administration of DNQX resulted in an increase of ACTH and corticosterone in plasma reaching maximal values at 15 min after drug injection. During immobilization stress, i.c.v. DNQX induced a mild reduction in plasma ACTH levels compared to those in aCSF pretreated rats. Corticosterone secretion was high throughout the whole period of stress exposure. These findings indicate that endogenous excitatory amino acids (EAA) acting at AMPA/kainate receptors may interfere with the control of ACTH release under both basal and stress conditions, but the mechanisms involved remain to be elucidated.