Stimulation of the hippocampal glutamate receptor systems induces stress-like responses.
OBJECTIVE
The hypothalamic-pituitary-adrenal (HPA) axis controls glucocorticoid secretion and is in turn controlled by a diverse set of afferents in the brain. However, the precise mechanisms underlying these actions remain to be elucidated. In our previous study, a lesion in the entorhinal cortex, which is the major provider of glutamatergic innervation to the hippocampus, significantly attenuated the elevation of adrenocorticotropic hormone (ACTH) in plasma during immobilization stress. In the present study, we examined the effects of microinjections of glutamatergic agonists into the hippocampus on plasma ACTH and glucose concentrations. We also studied the interactions between glutamate and acetylcholine in this response in the hippocampus.


METHODS
NMDA and AMPA subtypes of glutamate agonists were microinjected into the rat hippocampus, and ACTH and glucose levels in plasma were measured. The interaction between cholinergic and glutamatergic systems was investigated pharmacologically.


RESULTS
Both the NMDA and AMPA subtypes of glutamate agonists induced elevations of plasma ACTH and glucose levels in a dose-dependent fashion. These responses were independent of those induced by activation of the hippocampal cholinergic system.


CONCLUSIONS
Stimulation by the NMDA and AMPA subtypes of glutamate receptors in the hippocampus induced elevations of plasma ACTH and glucose, and these responses were independent of the cholinergic system.
Umegaki
Hiroyuki
H
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan. umegaki@med.nagoya-u.ac.jp
Yamamoto
Aki
A
Suzuki
Yusuke
Y
Iguchi
Akihisa
A
D000109:Acetylcholine / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D018683:Excitatory Amino Acid Agents / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000008:administration & dosage; D009388:Neostigmine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013312:Stress, Physiological / Q000139:chemically induced / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage
D001786:Blood Glucose; D002800:Cholinesterase Inhibitors; D018683:Excitatory Amino Acid Agents; D017470:Receptors, Glutamate; D009388:Neostigmine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000324:Adrenocorticotropic Hormone; D000109:Acetylcholine