EFFECTS OF EXCITATORY AMINO-ACIDS ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS OF THE NEONATAL RAT

Most stimuli that elicit a response by the hypothalamic-pituitary-adre nal (HPA) axis of adult rats fail to do so in infant rats aged 4-14 po stnatal days (pnd). This interval is termed the stress hyporesponsive period (SHRP). The present study examined the development of the HPA r esponse to the excitatory amino acids (EAAs), N-methyl-D-aspartic acid (NMDA) and kainic acid (KA), at 3 ages (i.e., pnd 6, 12, 18) during o r immediately after the SHRP. Results indicate that intraperitoneal (i .p.) administration of 2.5 mg/kg KA or 5 mg/kg NMDA is capable of indu cing age- and time-dependent elevations of ACTH and CORT, with KA bein g the more potent of the two EAAs. In contrast to other stimuli which are capable of eliciting an HPA response during the SHRP, NMDA and KA appear to possess more potent effects at earlier ages. Administration of lower doses of these EAAs did not elicit an HPA response. Pretreatm ent with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.69 mg/kg i.p.), a KA receptor-specific antagonist, attenuated the effects of KA. Thes e results suggest that KA exerts its effects via the KA receptor and t hat this receptor appears to be mature at both pnd 12 and Is. In contr ast, pretreatment with D,L-2-amino-5 phosphonovaleric acid (APV; 7.5 m g/kg i.p.), an NMDA receptor-specific antagonist, was only effective a t pnd 18 suggesting that the NMDA receptor is not yet mature at pnd 12 . Finally, EAAs induce age- and time-dependent behavioral modification s (i.e., hindpaw scratching and hyperlocomotion). These effects, howev er, appear to only contribute to, but not cause, the endocrine respons es.