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-adrenal (HPA) axis of adult rats fail to do so in infant rats aged 4-14 postnatal days (pnd). This interval is termed the stress hyporesponsive period (SHRP). The present study examined the development of the HPA response 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 or 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 inducing age- and time-dependent elevations of ACTH and CORT, with KA being 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. Pretreatment 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. These results suggest that KA exerts its effects via the KA receptor and that this receptor appears to be mature at both pnd 12 and 18. In contrast, pretreatment with D,L-2-amino-5 phosphonovaleric acid (APV; 7.5 mg/kg i.p.), an NMDA receptor-specific antagonist, was only effective at pnd 18 suggesting that the NMDA receptor is not yet mature at pnd 12. Finally, EAAs induce age- and time-dependent behavioral modifications (i.e., hindpaw scratching and hyperlocomotion). These effects, however, appear to only contribute to, but not cause, the endocrine responses.
Kent
S
S
Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, CA 94305-5095, USA.
Kernahan
S D
SD
Levine
S
S
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D000324:Adrenocorticotropic Hormone; D007608:Kainic Acid; D003345:Corticosterone