Control of ACTH secretion by excitatory amino acids: functional significance and clinical implications.

The involvement of excitatory amino acids in the control of ACTH release is well established. Activation of ionotropic glutamate receptors has a stimulatory effect on ACTH release, while the role of metabotropic receptors is not yet understood in detail. Glutamatergic regulation of ACTH release has a clear significance for the stress response and neuroendocrine functions during development. A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported in several psychiatric and neurological disorders. So far, only fractional indices on the clinical importance of the interaction between glutamate and ACTH secretion have been obtained in both preclinical and clinical studies. Some antidepressant drugs, such as tianeptine, which were found to modulate ACTH release, appear to interfere with brain glutamatergic system. Changes in ACTH and cortisol release may be of importance for mood stabilizing effects of antiepileptic drugs modulating glutamate release, such as lamotrigine. Brain glutamate and HPA axis interaction seems to be of importance in alcohol and drug abuse. Little information is available on ACTH release in response to glutamate-modulating drugs used in the treatment of schizophrenia and Alzheimer disease. Nevertheless, pharmacological interventions influencing interaction between glutamate and the HPA axis are promising treatment possibilities in psychiatry and neurology.