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.

MATERIALS AND 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.

CONCLUSION: 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.