Glucocorticoid-induced Enhancement of Extinction-from Animal Models to Clinical Trials

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2019 Jan 6

PMID 30610352

Citations 32

Authors

Dominique de Quervain

Oliver T Wolf

Benno Roozendaal

Affiliations

Soon will be listed here.

Abstract

Extensive evidence from both animal model and human research indicates that glucocorticoid hormones are crucially involved in modulating memory performance. Glucocorticoids, which are released during stressful or emotionally arousing experiences, enhance the consolidation of new memories, including extinction memory, but reduce the retrieval of previously stored memories. These memory-modulating properties of glucocorticoids have recently received considerable interest for translational purposes because strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias. Moreover, exposure-based psychological treatment of these disorders relies on successful fear extinction. In this review, we argue that glucocorticoid-based interventions facilitate fear extinction by reducing the retrieval of aversive memories and enhancing the consolidation of extinction memories. Several clinical trials have already indicated that glucocorticoids might be indeed helpful in the treatment of fear-related disorders.

Citing Articles

Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models.

Andero R Mol Psychiatry. 2025; .

PMID: 39890919 DOI: 10.1038/s41380-025-02910-8.

Systemic corticosterone enhances fear memory extinction in rats: Involvement of the infralimbic medial prefrontal cortex GABA and GABA receptors.

Omoumi S, Rashidy-Pour A, Seyedinia S, Tarahomi P, Sedaghat K, Vafaei A Brain Behav. 2024; 14(10):e70043.

PMID: 39344296 PMC: 11440020. DOI: 10.1002/brb3.70043.

Glucocorticoid receptor signaling in the brain and its involvement in cognitive function.

Su C, Huang T, Zhang M, Zhang Y, Zeng Y, Chen X Neural Regen Res. 2024; 20(9):2520-2537.

PMID: 39248182 PMC: 11801288. DOI: 10.4103/NRR.NRR-D-24-00355.

Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic-pituitary-adrenal-axis dysregulation: a study protocol description.

de Nooij L, Wirz L, Heling E, Pais M, Hendriks G, Verkes R Eur J Psychotraumatol. 2024; 15(1):2364441.

PMID: 38973398 PMC: 11232644. DOI: 10.1080/20008066.2024.2364441.

Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age.

Sanguino-Gomez J, Krugers H Neurobiol Stress. 2024; 31:100636.

PMID: 38883213 PMC: 11177066. DOI: 10.1016/j.ynstr.2024.100636.

References

Roozendaal B, Williams C, McGaugh J . Glucocorticoid receptor activation in the rat nucleus of the solitary tract facilitates memory consolidation: involvement of the basolateral amygdala. Eur J Neurosci. 1999; 11(4):1317-23. DOI: 10.1046/j.1460-9568.1999.00537.x. View

Kirschbaum C, Kudielka B, Gaab J, Schommer N, Hellhammer D . Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med. 1999; 61(2):154-62. DOI: 10.1097/00006842-199903000-00006. View

de Kloet E, Oitzl M, Joels M . Stress and cognition: are corticosteroids good or bad guys?. Trends Neurosci. 1999; 22(10):422-6. DOI: 10.1016/s0166-2236(99)01438-1. View

Roozendaal B, Nguyen B, Power A, McGaugh J . Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation. Proc Natl Acad Sci U S A. 1999; 96(20):11642-7. PMC: 18087. DOI: 10.1073/pnas.96.20.11642. View

McGaugh J . Memory--a century of consolidation. Science. 2000; 287(5451):248-51. DOI: 10.1126/science.287.5451.248. View

Henzen C, Suter A, Lerch E, Urbinelli R, Schorno X, Briner V . Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. Lancet. 2000; 355(9203):542-5. DOI: 10.1016/S0140-6736(99)06290-X. View

Sapolsky R, Romero L, Munck A . How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000; 21(1):55-89. DOI: 10.1210/edrv.21.1.0389. View

de Quervain D, Roozendaal B, Nitsch R, McGaugh J, Hock C . Acute cortisone administration impairs retrieval of long-term declarative memory in humans. Nat Neurosci. 2000; 3(4):313-4. DOI: 10.1038/73873. View

Roozendaal B . 1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology. 2000; 25(3):213-38. DOI: 10.1016/s0306-4530(99)00058-x. View

10.

Robinson T, Berridge K . The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction. 2000; 95 Suppl 2:S91-117. DOI: 10.1080/09652140050111681. View

11.

Sapolsky R . Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000; 57(10):925-35. DOI: 10.1001/archpsyc.57.10.925. View

12.

Delahanty D, Raimonde A, Spoonster E . Initial posttraumatic urinary cortisol levels predict subsequent PTSD symptoms in motor vehicle accident victims. Biol Psychiatry. 2000; 48(9):940-7. DOI: 10.1016/s0006-3223(00)00896-9. View

13.

Buchanan T, Lovallo W . Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology. 2001; 26(3):307-17. DOI: 10.1016/s0306-4530(00)00058-5. View

14.

Datson N, van der Perk J, de Kloet E, Vreugdenhil E . Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression. Eur J Neurosci. 2001; 14(4):675-89. DOI: 10.1046/j.0953-816x.2001.01685.x. View

15.

Wolf O, Convit A, McHugh P, Kandil E, Thorn E, De Santi S . Cortisol differentially affects memory in young and elderly men. Behav Neurosci. 2001; 115(5):1002-11. DOI: 10.1037//0735-7044.115.5.1002. View

16.

Schelling G, Briegel J, Roozendaal B, Stoll C, Rothenhausler H, Kapfhammer H . The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol Psychiatry. 2001; 50(12):978-85. DOI: 10.1016/s0006-3223(01)01270-7. View

17.

Yehuda R . Post-traumatic stress disorder. N Engl J Med. 2002; 346(2):108-14. DOI: 10.1056/NEJMra012941. View

18.

Pitman R, Sanders K, Zusman R, Healy A, Cheema F, Lasko N . Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002; 51(2):189-92. DOI: 10.1016/s0006-3223(01)01279-3. View

19.

McEwen B . Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci. 2002; 933:265-77. DOI: 10.1111/j.1749-6632.2001.tb05830.x. View

20.

McGaugh J, Roozendaal B . Role of adrenal stress hormones in forming lasting memories in the brain. Curr Opin Neurobiol. 2002; 12(2):205-10. DOI: 10.1016/s0959-4388(02)00306-9. View