Simultaneous Blockade of Two Glutamate Receptor Subtypes (NMDA and AMPA) Results in Stressor-Specific Inhibition of Prolactin and Corticotropin Release

Abstract

Many neurons express simultaneously two or more isotypes of glutamate receptors, so that pharmacological modulation of more than one receptor may be necessary to reveal the role of glutamate in mediating physiological processes. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic hormone (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-801, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rats were pretreated for 4–5 days and then exposed to stressful stimulation. Basal hormone levels were not affected by the antagonists. In male rats, combined, but not separate blockade of NMDA and AMPA/kainate subtypes of glutamate receptors prevented the rise in plasma PRL in response to footshock stress. In female rats, footshock-induced PRL release was inhibited even by separate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobilization or ether stress. Simultaneous blockade of NMDA and AMPA receptor subtypes resulted in a mild inhibition of immobilization-induced ACTH release without any effect on ACTH response to footshock or ether stress. The data suggest that involvement of glutamatergic pathways in neuroendocrine response during stress is selective for discrete stress stimuli and stress hormones. In addition a concerted action of glutamate on both NMDA and non-NMDA receptor subtypes is involved in the control of PRL release during footshock stress.

The stimuli-specific role of vasopressin in the hypothalamus–pituitary–adrenal axis response to stress

“…8 mA at 50 Hz for 1 s, repeated every 30 s for 5 min through a grid floor) as previously described (Zelena et al 1999c). Control rats were transferred to the same box without electrical impulses.…”

Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men

“…However, different stress stimuli have been shown to provoke stressor-specific counter-regulatory responses that are possibly mediated via different central nervous pathways. Whereas the blockade of AMPA and NMDA receptors suppresses the ACTH response to immobilisation stress in rats, the neuroendocrine response to foot shock or ether stress is not affected by blockade of these receptors [5]. Our finding that blocking AMPA receptors by caroverine does not alter the neuroendocrine counter-regulatory response to hypoglycaemia suggests that in humans neuroendocrine responses to this specific metabolic stressor are mediated via AMPA-independent pathways.…”

“…As the glutamate signal is conveyed by amino-3-hydroxy-5-methyl-4-isoxazol propionate (AMPA) receptor subtypes, whereas NMDA receptors are thought to play a role in inducing or modulating the plasticity of AMPA receptor-mediated transmission, the above finding raises the question as to what role AMPA receptors play in the acute neuroendocrine and neurocognitive response to hypoglycaemia in humans. In rats, pharmacological blockade of AMPA receptors diminished the neuroendocrine response to immobilisation stress [5][6][7]. Against this background, we assessed neuroglycopenic and autonomic symptoms, and neuroendocrine responses to insulin-induced hypoglycaemia in healthy men after pretreatment with the AMPA receptor antagonist caroverine.…”

Inhibition of Stress-Induced Adrenocorticotropin and Prolactin Secretion Mediating Hypophysiotropic Factors by Antagonist of AMPA Type Glutamate Receptor

“…Jezova et al [19] reported that ACTH secretion in response to immobilization stress was inhibited by p r e t r e a t m e n t w i t h a c e n t r a l l y a c t i n g noncompetitive NMDA antagonist MK-801, but not by a competitive NMDA receptor antagonist, CPP. Zelena et al [18] also described that blockade of the combination of the NMDA and AMPA/kainate subtypes of glutamate receptor by MK-801 and GYKI 52466 prevented the rise in plasma prolactin in response to footshock stress in male rats. These reports indicated that the NMDA and AMPA receptors play important roles in regulation of ACTH and prolactin release in response to stress.…”

“…Simultaneous blockade of NMDA and AMPA/kainate receptors results in mild inhibition of immobilization-induced ACTH release [18]. Jezova et al [19] reported that ACTH secretion in response to immobilization stress was inhibited by p r e t r e a t m e n t w i t h a c e n t r a l l y a c t i n g noncompetitive NMDA antagonist MK-801, but not by a competitive NMDA receptor antagonist, CPP.…”