Cited by 914Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior

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Neuroendocrine pharmacology of stress

Carrasco, Gonzalo A, Van de Kar, Louis D·2003·European Journal of Pharmacology

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Abstract

Exposure to hostile conditions initiates responses organized to enhance the probability of survival. These coordinated responses, known as stress responses, are composed of alterations in behavior, autonomic function and the secretion of multiple hormones. The activation of the renin-angiotensin system and the hypothalamic-pituitary-adrenocortical axis plays a pivotal role in the stress response. Neuroendocrine components activated by stressors include the increased secretion of epinephrine and norepinephrine from the sympathetic nervous system and adrenal medulla, the release of corticotropin-releasing factor (CRF) and vasopressin from parvicellular neurons into the portal circulation, and seconds later, the secretion of pituitary adrenocorticotropin (ACTH), leading to secretion of glucocorticoids by the adrenal gland. Corticotropin-releasing factor coordinates the endocrine, autonomic, behavioral and immune responses to stress and also acts as a neurotransmitter or neuromodulator in the amygdala, dorsal raphe nucleus, hippocampus and locus coeruleus, to integrate brain multi-system responses to stress. This review discussed the role of classical mediators of the stress response, such as corticotropin-releasing factor, vasopressin, serotonin (5-hydroxytryptamine or 5-HT) and catecholamines. Also discussed are the roles of other neuropeptides/neuromodulators involved in the stress response that have previously received little attention, such as substance P, vasoactive intestinal polypeptide, neuropeptide Y and cholecystokinin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABA(A), histamine and serotonin receptors have been used to attenuate the neuroendocrine response to stressors. The neuroendocrine information for these drugs is still incomplete; however, they are a new class of potential antidepressant and anxiolytic drugs that offer new therapeutic approaches to treating anxiety disorders. The studies described in this review suggest that multiple brain mechanisms are responsible for the regulation of each hormone and that not all hormones are regulated by the same neural circuits. In particular, the renin-angiotensin system seems to be regulated by different brain mechanisms than the hypothalamic-pituitary-adrenal system. This could be an important survival mechanism to ensure that dysfunction of one neurotransmitter system will not endanger the appropriate secretion of hormones during exposure to adverse conditions. The measurement of several hormones to examine the mechanisms underlying the stress response and the effects of drugs and lesions on these responses can provide insight into the nature and location of brain circuits and neurotransmitter receptors involved in anxiety and stress.

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Authors: Carrasco, G. A., & Van de Kar, L. D.
Affiliations: Loyola University Chicago (US)
ORCID: Carrasco, Gonzalo A
Venue: European Journal of Pharmacology
Publisher: Elsevier BV
Published: 2003-02
Volume: 463
Issue: 1-3
Pages: 235-272
ISSN: 0014-2999 (ISSN-L)
DOI: 10.1016/s0014-2999(03)01285-8
OpenAlex: W1971277989
Cited by: 914
References: 656
Citations by year: 2026: 7 · 2025: 11 · 2024: 24 · 2023: 27 · 2022: 29 · 2021: 37 · 2020: 32 · 2019: 30 · 2018: 36 · 2017: 27 · 2016: 36 · 2015: 34 · 2014: 43 · 2013: 64 · 2012: 49
FWCI: 21.36
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Journal of Pharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (R01DA013669, DA 13669)
National Institute of Neurological Disorders and Stroke (NS34153)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Keywords: stress response, neuroendocrine regulation, corticotropin-releasing factor, vasopressin, renin-angiotensin system, hypothalamic-pituitary-adrenal axis, catecholamines, serotonin, substance P, vasoactive intestinal peptide, neuropeptide Y, cholecystokinin, benzodiazepines, anxiolytics, antidepressants, anxiety disorders, glucocorticoids, ACTH, sympathetic nervous system, adrenal medulla
MeSH terms: Amygdala, Animals, Brain Chemistry, Endocrine System, Humans, Hypothalamus, Neurosecretory Systems, Stress, Physiological, Neurotransmitter Agents

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