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 control a lpha-amino-3-hydroxy-5-methyl-4-isozazole propionate (AMPA)/kainate ty pe of glutamate receptors in the control of ACTH and corticosterone re lease under basal and stress conditions. AMPA/kainate competitive rece ptor antagonist 6,7-dinitroquinoxaline-2.3-dione (DNQX), which does no t penetrate the blood-brain barrier, was administered intracerebrovent ricularly (i.c.v.). A modified method for i.c.v drug administration in conscious freely moving rats was employed. DNQX or artificial cerebro spinal fluid (aCSF) was injected into lateral ventricle through a thin polyethylene cannula with a steel needle to the end which was inserte d and moved via large polyethylene cannula to the guide stainless stee l cannula. This procedure was performed out of the cage. ACTH and cort icosterone release under basal conditions and during immobilization st ress 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 com pared to those in aCSF pretreated rats. Corticosterone secretion was h igh throughout the whole period of stress exposure. These finding indi cate that endogenous excitatory amino acids (EAA) acting at AMPA/kaina te receptors may interfere with the control of ACTH release under both basal and stress conditions, but the mechanisms involved remain to be elucidated.