Chemogenetic activation of CRF neurons as a model of chronic stress produces sex-specific physiological and behavioral effects.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
13 Oct 2023
13 Oct 2023
Historique:
received:
08
06
2023
accepted:
07
09
2023
revised:
29
08
2023
medline:
14
10
2023
pubmed:
14
10
2023
entrez:
13
10
2023
Statut:
aheadofprint
Résumé
Trauma and chronic stress exposure are the strongest predictors of lifetime neuropsychiatric disease presentation. These disorders often have significant sex biases, with females having higher incidences of affective disorders such as major depression, anxiety, and PTSD. Understanding the mechanisms by which stress exposure heightens disease vulnerability is essential for developing novel interventions. Current rodent stress models consist of a battery of sensory, homeostatic, and psychological stressors that are ultimately integrated by corticotropin-releasing factor (CRF) neurons to trigger corticosteroid release. These stress paradigms, however, often differ between research groups in the type, timing, and duration of stressors utilized. These inconsistencies, along with the variability of individual animals' perception and response to each stressor, present challenges for reproducibility and translational relevance. Here, we hypothesized that a more direct approach using chemogenetic activation of CRF neurons would recapitulate the effects of traditional stress paradigms and provide a high-throughput method for examining stress-relevant phenotypes. Using a transgenic approach to express the Gq-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD) receptor hM3Dq in CRF-neurons, we found that the DREADD ligand clozapine-N-oxide (CNO) produced an acute and robust activation of the hypothalamic-pituitary-adrenal (HPA) axis, as predicted. Interestingly, chronic treatment with this method of direct CRF activation uncovered a novel sex-specific dissociation of glucocorticoid levels with stress-related outcomes. Despite hM3Dq-expressing females producing greater corticosterone levels in response to CNO than males, hM3Dq-expressing males showed significant typical physiological stress sensitivity with reductions in body and thymus weights. hM3Dq-expressing females while resistant to the physiological effects of chronic CRF activation, showed significant increases in baseline and fear-conditioned freezing behaviors. These data establish a novel mouse model for interrogating stress-relevant phenotypes and highlight sex-specific stress circuitry distinct for physiological and limbic control that may underlie disease risk.
Identifiants
pubmed: 37833589
doi: 10.1038/s41386-023-01739-5
pii: 10.1038/s41386-023-01739-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : 097093
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
Références
Grant JK, Forrest APM, Symington T. The secretion of cortisol and corticosterone by the human adrenal cortex. Acta Endocrinologica (Nor). 1957;26:195–203.
Brown KI. The validity of using plasma corticosterone as a measure of stress in the Turkey. Proc Soc Exp Biol Med. 1961;107:538–42.
doi: 10.3181/00379727-107-26680
Triller H, Birmingham MK. Steroid production by incubated mouse adrenals: I. Characterization of steroid fractions. Gen Comp Endocrinol. 1965;5:618–23.
pubmed: 5848004
doi: 10.1016/0016-6480(65)90081-X
Estergreen VL, Venkataseshu GK. Positive identification of corticosterone and cortisol in jugular plasma of dairy cattle. Steroids 1967;10:83–92.
pubmed: 6058016
doi: 10.1016/0039-128X(67)90072-4
Spiess J, Rivier J, Rivier C, Vale W. Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc Natl Acad Sci 1981;78:6517–21.
pubmed: 6273874
pmcid: 349071
doi: 10.1073/pnas.78.10.6517
Rivier J, Spiess J, Vale W. Characterization of rat hypothalamic corticotropin-releasing factor. Proc Natl Acad Sci 1983;80:4851–5.
pubmed: 6603620
pmcid: 384143
doi: 10.1073/pnas.80.15.4851
Esch F, Ling N, Bohlen P, Baird A, Benoit R, Guillemin R. Isolation and characterization of the bovine hypothalamic corticotropin-releasing factor. Biochemical Biophysical Res Commun. 1984;122:899–905.
doi: 10.1016/0006-291X(84)91175-6
Stenzel-Poore MP, Heldwein KA, Stenzel P, Lee S, Vale WW. Characterization of the genomic corticotropin-releasing factor (CRF) gene from Xenopus laevis: two members of the CRF family exist in amphibians. Mol Endocrinol. 1992;6:1716–24.
pubmed: 1448118
Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 1981;213:1394–7.
pubmed: 6267699
doi: 10.1126/science.6267699
Rivier C, Vale W. Effects of corticotropin-releasing factor, neurohypophyseal peptides, and catecholamines on pituitary function. Fed Proc. 1985;44:189–95.
pubmed: 2981740
Aguilera G, Liu Y. The molecular physiology of CRH neurons. Front Neuroendocrinol. 2012;33:67–84.
pubmed: 21871477
doi: 10.1016/j.yfrne.2011.08.002
Deussing JM, Chen A. The corticotropin-releasing factor family: physiology of the stress response. Physiol Rev. 2018;98:2225–86.
pubmed: 30109816
doi: 10.1152/physrev.00042.2017
Gray TS. Amygdaloid CRF pathways. Role in autonomic, neuroendocrine, and behavioral responses to stress. Ann N. Y Acad Sci. 1993;697:53–60.
pubmed: 8257022
doi: 10.1111/j.1749-6632.1993.tb49922.x
Kalin NH, Takahashi LK, Chen F-L. Restraint stress increases corticotropin-releasing hormone mRNA content in the amygdala and paraventricular nucleus. Brain Res. 1994;656:182–6.
pubmed: 7804835
doi: 10.1016/0006-8993(94)91382-X
Gray TS, Bingaman EW. The amygdala: corticotropin-releasing factor, steroids, and stress. Crit Rev Neurobiol. 1996;10:155–68.
pubmed: 8971127
doi: 10.1615/CritRevNeurobiol.v10.i2.10
Olschowka JA, O’Donohue TL, Mueller GP, Jacobowitz DM. The distribution of corticotropin releasing factor-like immunoreactive neurons in rat brain. Peptides 1982;3:995–1015.
pubmed: 6984756
doi: 10.1016/0196-9781(82)90071-7
Cummings S, Elde R, Ells J, Lindall A. Corticotropin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study. J Neurosci. 1983;3:1355–68.
pubmed: 6345725
pmcid: 6564441
doi: 10.1523/JNEUROSCI.03-07-01355.1983
Sakanaka M, Shibasaki T, Lederis K. Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex. Brain Res. 1986;382:213–38.
pubmed: 2428439
doi: 10.1016/0006-8993(86)91332-6
Choi DC, Furay AR, Evanson NK, Ostrander MM, Ulrich-Lai YM, Herman JP. Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic–pituitary–adrenal axis activity: implications for the integration of limbic inputs. J Neurosci. 2007;27:2025–34.
pubmed: 17314298
pmcid: 6673539
doi: 10.1523/JNEUROSCI.4301-06.2007
Jankord R, Herman JP. Limbic regulation of hypothalamo-pituitary-adrenocortical function during acute and chronic stress. Ann N. Y Acad Sci. 2008;1148:64–73.
pubmed: 19120092
pmcid: 2637449
doi: 10.1196/annals.1410.012
Sawchenko PE, Swanson LW. The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat. J Comp Neurol. 1983;218:121–44.
pubmed: 6886068
doi: 10.1002/cne.902180202
Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, et al. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo–pituitary–adrenocortical responsiveness. Front Neuroendocrinol. 2003;24:151–80.
pubmed: 14596810
doi: 10.1016/j.yfrne.2003.07.001
Bale TL, Vale WW. CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol. 2004;44:525–57.
pubmed: 14744257
doi: 10.1146/annurev.pharmtox.44.101802.121410
Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009;10:397–409.
pubmed: 19469025
pmcid: 4240627
doi: 10.1038/nrn2647
Joëls M, Baram TZ. The neuro-symphony of stress. Nat Rev Neurosci. 2009;10:459–66.
pubmed: 19339973
pmcid: 2844123
doi: 10.1038/nrn2632
Herman JP, McKlveen JM, Ghosal S, Kopp B, Wulsin A, Makinson R, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Compr Physiol. 2016;6:603–21.
pubmed: 27065163
pmcid: 4867107
doi: 10.1002/cphy.c150015
Nemeroff CB. The Role of Corticotropin-Releasing Factor in the Pathogenesis of Major Depression. Pharmacopsychiatry 1988;21:76–82.
pubmed: 3293091
doi: 10.1055/s-2007-1014652
Nemeroff CB, Widerlöv E, Bissette G, Walléus H, Karlsson I, Eklund K, et al. Elevated Concentrations of CSF Corticotropin-Releasing Factor-Like Immunoreactivity in Depressed Patients. Science 1984;226:1342–4.
pubmed: 6334362
doi: 10.1126/science.6334362
Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM, et al. Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder. Am J Psychiatry. 1997;154:624–9.
pubmed: 9137116
pmcid: 3233756
doi: 10.1176/ajp.154.5.624
Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999;160:1–12.
pubmed: 9854171
doi: 10.1677/joe.0.1600001
Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002;34:13–25.
pubmed: 11931738
doi: 10.1016/S0896-6273(02)00653-0
Bale TL. Stress sensitivity and the development of affective disorders. Hormones Behav. 2006;50:529–33.
doi: 10.1016/j.yhbeh.2006.06.033
Blank T, Spiess J Corticotropin-Releasing Factor (CRF) and CRF-Related Peptides – a Linkage Between Stress and Anxiety. Stress - From Molecules to Behavior, John Wiley & Sons, Ltd; 2009. p. 151-65.
Valentino RJ, Page ME, Curtis AL. Activation of noradrenergic locus coeruleus neurons by hemodynamic stress is due to local release of corticotropin-releasing factor. Brain Res. 1991;555:25–34.
pubmed: 1933327
doi: 10.1016/0006-8993(91)90855-P
Van Bockstaele EJ, Colago EEO, Valentino RJ. Amygdaloid corticotropin-releasing factor targets locus coeruleus dendrites: substrate for the co-ordination of emotional and cognitive limbs of the stress response. J Neuroendocrinol. 1998;10:743–58.
pubmed: 9792326
doi: 10.1046/j.1365-2826.1998.00254.x
Van Bockstaele EJ, Peoples J, Valentino RJ. Anatomic basis for differential regulation of the rostrolateral peri–locus coeruleus region by limbic afferents. Biol Psychiatry. 1999;46:1352–63.
pubmed: 10578450
doi: 10.1016/S0006-3223(99)00213-9
Flak JN, Myers B, Solomon MB, McKlveen JM, Krause EG, Herman JP. Role of paraventricular nucleus-projecting norepinephrine/epinephrine neurons in acute and chronic stress. Eur J Neurosci. 2014;39:1903–11.
pubmed: 24766138
pmcid: 4538596
doi: 10.1111/ejn.12587
McCall JG, Al-Hasani R, Siuda ER, Hong DY, Norris AJ, Ford CP, et al. CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety. Neuron 2015;87:605–20.
pubmed: 26212712
pmcid: 4529361
doi: 10.1016/j.neuron.2015.07.002
Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 1997;134:319–29.
pubmed: 9452163
doi: 10.1007/s002130050456
Schmidt MV, Sterlemann V, Ganea K, Liebl C, Alam S, Harbich D, et al. Persistent neuroendocrine and behavioral effects of a novel, etiologically relevant mouse paradigm for chronic social stress during adolescence. Psychoneuroendocrinology 2007;32:417–29.
pubmed: 17449187
doi: 10.1016/j.psyneuen.2007.02.011
Jaggi AS, Bhatia N, Kumar N, Singh N, Anand P, Dhawan R. A review on animal models for screening potential anti-stress agents. Neurol Sci. 2011;32:993–1005.
pubmed: 21927881
doi: 10.1007/s10072-011-0770-6
Schmidt MV, Wang X-D, Meijer OC. Early life stress paradigms in rodents: potential animal models of depression? Psychopharmacology 2011;214:131–40.
pubmed: 21086114
doi: 10.1007/s00213-010-2096-0
Willner P. Reliability of the chronic mild stress model of depression: A user survey. Neurobiol Stress 2017;6:68–77.
pubmed: 28229110
doi: 10.1016/j.ynstr.2016.08.001
Antoniuk S, Bijata M, Ponimaskin E, Wlodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev. 2019;99:101–16.
pubmed: 30529362
doi: 10.1016/j.neubiorev.2018.12.002
Atrooz F, Alkadhi KA, Salim S. Understanding stress: Insights from rodent models. Curr Res Neurobiol. 2021;2:100013.
pubmed: 36246514
pmcid: 9559100
doi: 10.1016/j.crneur.2021.100013
Aloisi AM, Steenbergen HL, Van De Poll NE, Farabollini F. Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat. Physiol Behav. 1994;55:789–93.
pubmed: 8022895
doi: 10.1016/0031-9384(94)90061-2
Dalla C, Pitychoutis PM, Kokras N, Papadopoulou-Daifoti Z Sex Differences in Response to Stress and Expression of Depressive-Like Behaviours in the Rat. In: Neill JC, Kulkarni J, editors. Biological Basis of Sex Differences in Psychopharmacology, Berlin, Heidelberg: Springer; 2011. p. 97–118.
Franceschelli A, Herchick S, Thelen C, Papadopoulou-Daifoti Z, Pitychoutis PM. Sex differences in the chronic mild stress model of depression. Behavioural Pharmacol. 2014;25:372.
doi: 10.1097/FBP.0000000000000062
Johnson A, Rainville JR, Rivero-Ballon GN, Dhimitri K, Hodes GE. Testing the limits of sex differences using variable stress. Neuroscience 2021;454:72–84.
pubmed: 31917340
doi: 10.1016/j.neuroscience.2019.12.034
Lopez J, Bagot RC. Defining valid chronic stress models for depression with female rodents. Biol Psychiatry. 2021;90:226–35.
pubmed: 33965195
doi: 10.1016/j.biopsych.2021.03.010
Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci 2007;104:5163–8.
pubmed: 17360345
pmcid: 1829280
doi: 10.1073/pnas.0700293104
Alexander GM, Rogan SC, Abbas AI, Armbruster BN, Pei Y, Allen JA, et al. Remote control of neuronal activity in transgenic mice expressing evolved g protein-coupled receptors. Neuron 2009;63:27–39.
pubmed: 19607790
pmcid: 2751885
doi: 10.1016/j.neuron.2009.06.014
Morrison KE, Epperson CN, Sammel MD, Ewing G, Podcasy JS, Hantsoo L, et al. Preadolescent adversity programs a disrupted maternal stress reactivity in humans and mice. Biol Psychiatry. 2017;81:693–701.
pubmed: 27776734
doi: 10.1016/j.biopsych.2016.08.027
Hesselgrave N, Troppoli TA, Wulff AB, Cole AB, Thompson SM. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc Natl Acad Sci 2021;118:e2022489118.
pubmed: 33850049
pmcid: 8092378
doi: 10.1073/pnas.2022489118
Troppoli TA, Zanos P, Georgiou P, Gould TD, Rudolph U, Thompson SM. Negative allosteric modulation of gamma-aminobutyric acid a receptors at α5 subunit–containing benzodiazepine sites reverses stress-induced anhedonia and weakened synaptic function in mice. Biol Psychiatry. 2022;92:216–26.
pubmed: 35120711
doi: 10.1016/j.biopsych.2021.11.024
Flak JN, Ostrander MM, Tasker JG, Herman JP. Chronic stress-induced neurotransmitter plasticity in the PVN. J Comp Neurol. 2009;517:156–65.
pubmed: 19731312
pmcid: 4539130
doi: 10.1002/cne.22142
Herman J. Neural control of chronic stress adaptation. Front Behav Neurosci. 2013;7:61.
Blanchard RJ, Nikulina JN, Sakai RR, McKittrick C, McEwen B, Blanchard DC. Behavioral and endocrine change following chronic predatory stress. Physiol Behav. 1998;63:561–9.
pubmed: 9523899
doi: 10.1016/S0031-9384(97)00508-8
Cabib S, Kempf E, Schleef C, Mele A, Puglisi-Allegra S. Different effects of acute and chronic stress on two dopamine-mediated behaviors in the mouse. Physiol Behav. 1988;43:223–7.
pubmed: 3212060
doi: 10.1016/0031-9384(88)90242-9
Schmidt MV, Sterlemann V, Müller MB. Chronic stress and individual vulnerability. Ann N. Y Acad Sci. 2008;1148:174–83.
pubmed: 19120107
doi: 10.1196/annals.1410.017
Taliaz D, Loya A, Gersner R, Haramati S, Chen A, Zangen A. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. J Neurosci. 2011;31:4475–83.
pubmed: 21430148
pmcid: 6622886
doi: 10.1523/JNEUROSCI.5725-10.2011
Checkley S. The neuroendocrinology of depression and chronic stress. Br Med Bull. 1996;52:597–617.
pubmed: 8949260
doi: 10.1093/oxfordjournals.bmb.a011570
Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE, et al. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet. 2000;24:410–4.
pubmed: 10742108
doi: 10.1038/74263
Koob GF, Heinrichs SC. A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res. 1999;848:141–52.
pubmed: 10612706
doi: 10.1016/S0006-8993(99)01991-5
Sutton RE, Koob GF, Le Moal M, Rivier J, Vale W. Corticotropin releasing factor produces behavioural activation in rats. Nature 1982;297:331–3.
pubmed: 6978997
doi: 10.1038/297331a0
Stenzel-Poore MP, Heinrichs SC, Rivest S, Koob GF, Vale WW. Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior. J Neurosci. 1994;14:2579–84.
pubmed: 8182429
pmcid: 6577466
doi: 10.1523/JNEUROSCI.14-05-02579.1994
Bale TL, Epperson CN. Sex differences and stress across the lifespan. Nat Neurosci. 2015;18:1413–20.
pubmed: 26404716
pmcid: 4620712
doi: 10.1038/nn.4112
Franco AJ, Chen C, Scullen T, Zsombok A, Salahudeen AA, Di S, et al. Sensitization of the Hypothalamic-Pituitary-Adrenal Axis in a Male Rat Chronic Stress Model. Endocrinology 2016;157:2346–55.
pubmed: 27054552
pmcid: 4891782
doi: 10.1210/en.2015-1641
Tasker JG, Joëls M The Synaptic Physiology of the Central Nervous System Response to Stress. In: Russell J, Shipston M, editors. Neuroendocrinology of Stress, Chichester, UK: John Wiley & Sons, Ltd; 2015. p. 43–70.
Selye H. The general adaptation syndrome and the diseases of adaptation. J Clin Endocrinol Metab. 1946;6:117–230.
pubmed: 21025115
doi: 10.1210/jcem-6-2-117
McEwen BS. Stress, adaptation, and disease: allostasis and allostatic load. Ann N. Y Acad Sci. 1998;840:33–44.
pubmed: 9629234
doi: 10.1111/j.1749-6632.1998.tb09546.x
McEwen BS, Akil H. Revisiting the stress concept: implications for affective disorders. J Neurosci. 2020;40:12–21.
pubmed: 31896560
pmcid: 6939488
doi: 10.1523/JNEUROSCI.0733-19.2019
Bains JS, Cusulin JIW, Inoue W. Stress-related synaptic plasticity in the hypothalamus. Nat Rev Neurosci. 2015;16:377–88.
pubmed: 26087679
doi: 10.1038/nrn3881
López JF, Akil H, Watson SJ. Neural circuits mediating stress. Biol Psychiatry. 1999;46:1461–71.
pubmed: 10599476
doi: 10.1016/S0006-3223(99)00266-8
Morrison KE, Cole AB, Kane PJ, Meadows VE, Thompson SM, Bale TL. Pubertal adversity alters chromatin dynamics and stress circuitry in the pregnant brain. Neuropsychopharmacology 2020;45:1263–71.
pubmed: 32045935
pmcid: 7297802
doi: 10.1038/s41386-020-0634-y
Cole AB, Montgomery K, Bale TL, Thompson SM. What the hippocampus tells the HPA axis: Hippocampal output attenuates acute stress responses via disynaptic inhibition of CRF+ PVN neurons. Neurobiol Stress 2022;20:100473.
pubmed: 35982732
pmcid: 9379952
doi: 10.1016/j.ynstr.2022.100473
Orth DN, Jackson RV, DeCherney GS, DeBold CR, Alexander AN, Island DP, et al. Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol. 1983. https://www.jci.org/articles/view/110804/scanned-page/590 . Accessed 29 April 2023.
Veissier I, van Reenen CG, Andanson S, Leushuis IE. Adrenocorticotropic hormone and cortisol in calves after corticotropin-releasing hormone. J Anim Sci. 1999;77:2047–53.
pubmed: 10461980
doi: 10.2527/1999.7782047x
Babb JA, Masini CV, Day HEW, Campeau S. Sex differences in activated CRF neurons within stress-related neurocircuitry and HPA axis hormones following restraint in rats. Neuroscience 2013;234:40–52.
pubmed: 23305762
doi: 10.1016/j.neuroscience.2012.12.051
Handa RJ, Burgess LH, Kerr JE, O’Keefe JA. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis. Hormones Behav. 1994;28:464–76.
doi: 10.1006/hbeh.1994.1044
Handa RJ, Nunley KM, Lorens SA, Louie JP, McGivern RF, Bollnow MR. Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors. Physiol Behav. 1994;55:117–24.
pubmed: 8140154
doi: 10.1016/0031-9384(94)90018-3
Bingaman EW, Magnuson DJ, Gray TS, Handa RJ. Androgen inhibits the increases in hypothalamic corticotropin-releasing hormone (CRH) and CRH-lmmunoreactivity following gonadectomy. NEN. 1994;59:228–34.
Haas DA, George SR. Gonadal regulation of corticotropin-releasing factor immunoreactivity in hypothalamus. Brain Res Bull. 1988;20:361–7.
pubmed: 3284608
doi: 10.1016/0361-9230(88)90065-2
Panagiotakopoulos L, Neigh GN. Development of the HPA axis: Where and when do sex differences manifest? Front Neuroendocrinol. 2014;35:285–302.
pubmed: 24631756
doi: 10.1016/j.yfrne.2014.03.002
Gomez JL, Bonaventura J, Lesniak W, Mathews WB, Sysa-Shah P, Rodriguez LA, et al. Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Science 2017;357:503–7.
pubmed: 28774929
pmcid: 7309169
doi: 10.1126/science.aan2475
Roth BL. DREADDs for neuroscientists. Neuron 2016;89:683–94.
pubmed: 26889809
pmcid: 4759656
doi: 10.1016/j.neuron.2016.01.040
Jendryka M, Palchaudhuri M, Ursu D, van der Veen B, Liss B, Kätzel D, et al. Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice. Sci Rep. 2019;9:4522.
pubmed: 30872749
pmcid: 6418145
doi: 10.1038/s41598-019-41088-2
Chambers KC, Sengstake CB. Sexually dimorphic extinction of a conditioned taste aversion in rats. Anim Learn Behav. 1976;4:181–5.
pubmed: 964443
doi: 10.3758/BF03214032
Dacanay RJ, Mastropaolo JP, Olin DA, Riley AL. Sex differences in taste aversion learning: An analysis of the minimal effective dose. Neurobehavioral Toxicol Teratol. 1984;6:9–11.
Dalla C, Shors TJ. Sex differences in learning processes of classical and operant conditioning. Physiol Behav. 2009;97:229–38.
pubmed: 19272397
pmcid: 2699937
doi: 10.1016/j.physbeh.2009.02.035
Randall-Thompson JF, Riley AL. Morphine-induced conditioned taste aversions: assessment of sexual dimorphism. Pharmacol Biochem Behav. 2003;76:373–81.
pubmed: 14592690
doi: 10.1016/j.pbb.2003.08.010
Bernanke A, Burnette E, Murphy J, Hernandez N, Zimmerman S, Walker QD, et al. Behavior and Fos activation reveal that male and female rats differentially assess affective valence during CTA learning and expression. PLOS ONE. 2021;16:e0260577.
pubmed: 34898621
pmcid: 8668140
doi: 10.1371/journal.pone.0260577
Levine AS, Morley JE. Stress-induced eating in rats. Am J Physiol. 1981;241:R72–76.
pubmed: 7195655
Michajlovskij N, Lichardus B, Kvetnanský R, Ponec J. Effect of acute and repeated immobilization stress on food and water intake, urine output and vasopressin changes in rats. Endocrinol Exp. 1988;22:143–57.
pubmed: 3265380
Vallès A, Martí O, García A, Armario A. Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats. Am J Physiol-Regulatory, Integr Comp Physiol. 2000;279:R1138–R1144.
doi: 10.1152/ajpregu.2000.279.3.R1138
Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980;284:555–6.
pubmed: 6245367
doi: 10.1038/284555a0
Magarin˜os AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Comparison of stressors. Neuroscience 1995;69:83–88.
pubmed: 8637635
doi: 10.1016/0306-4522(95)00256-I
Tarcic N, Ovadia H, Weiss DW, Weidenfeld J. Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids. J Neuroimmunol. 1998;82:40–46.
pubmed: 9526844
doi: 10.1016/S0165-5728(97)00186-0
Ehlers CL, Chaplin RI, Kaneko WM. Effects of chronic corticosterone treatment on electrophysiological and behavioral measures in the rat. Psychoneuroendocrinology 1992;17:691–9.
pubmed: 1287687
doi: 10.1016/0306-4530(92)90028-6
Pavlovska-Teglia G, Stodulski G, Svendsen L, Dalton K, Hau J. Effect of oral corticosterone administration on locomotor development of neonatal and juvenile rats. Exp Physiol. 1995;80:469–75.
pubmed: 7640011
doi: 10.1113/expphysiol.1995.sp003861
Kalynchuk LE, Gregus A, Boudreau D, Perrot-Sinal TS. Corticosterone increases depression-like behavior, with some effects on predator odor-induced defensive behavior, in male and female rats. Behav Neurosci. 2004;118:1365–77.
pubmed: 15598145
doi: 10.1037/0735-7044.118.6.1365
Gregus A, Wintink AJ, Davis AC, Kalynchuk LE. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behavioural Brain Res. 2005;156:105–14.
doi: 10.1016/j.bbr.2004.05.013
Murray F, Smith DW, Hutson PH. Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol. 2008;583:115–27.
pubmed: 18289522
doi: 10.1016/j.ejphar.2008.01.014
Kott JM, Mooney-Leber SM, Shoubah FA, Brummelte S. Effectiveness of different corticosterone administration methods to elevate corticosterone serum levels, induce depressive-like behavior, and affect neurogenesis levels in female rats. Neuroscience 2016;312:201–14.
pubmed: 26556064
doi: 10.1016/j.neuroscience.2015.11.006
Mekiri M, Gardier AM, David DJ, Guilloux J-P. Chronic corticosterone administration effects on behavioral emotionality in female c57bl6 mice. Exp Clin Psychopharmacol. 2017;25:94–104.
pubmed: 28287792
doi: 10.1037/pha0000112
Shahanoor Z, Sultana R, Baker MR, Romeo RD. Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence. Psychoneuroendocrinology 2017;86:218–24.
pubmed: 29020649
doi: 10.1016/j.psyneuen.2017.10.001
Bullitt E. Expression of C-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol. 1990;296:517–30.
pubmed: 2113539
doi: 10.1002/cne.902960402
Sharp FR, Sagar SM, Hicks K, Lowenstein D, Hisanaga K. c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress. J Neurosci. 1991;11:2321–31.
pubmed: 1908006
pmcid: 6575523
doi: 10.1523/JNEUROSCI.11-08-02321.1991
Cullinan WE, Herman JP, Battaglia DF, Akil H, Watson SJ. Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience 1995;64:477–505.
pubmed: 7700534
doi: 10.1016/0306-4522(94)00355-9
Hodes GE, Epperson CN. Sex differences in vulnerability and resilience to stress across the life span. Biol Psychiatry. 2019;86:421–32.
pubmed: 31221426
pmcid: 8630768
doi: 10.1016/j.biopsych.2019.04.028
Goel N, Bale TL. Examining the intersection of sex and stress in modelling neuropsychiatric disorders. J Neuroendocrinol. 2009;21:415–20.
pubmed: 19187468
pmcid: 2716060
doi: 10.1111/j.1365-2826.2009.01843.x
Board F, Wadeson R, Persky H. Depressive affect and endocrine functions: blood levels of adrenal cortex and thyroid hormones in patients suffering from depressive reactions. AMA Arch Neurol Psychiatry 1957;78:612–20.
pubmed: 13478217
doi: 10.1001/archneurpsyc.1957.02330420072015
Gibbons JL, McHugh PR. Plasma cortisol in depressive illness. J Psychiatr Res. 1962;1:162–71.
pubmed: 13947658
doi: 10.1016/0022-3956(62)90006-7
Carroll BJ, Martin FIR, Davies B. Pituitary-Adrenal function in depression. Lancet. 1968;291:1373–4.
doi: 10.1016/S0140-6736(68)92072-2
Insel TR, Kalin NH, Guttmacher LB, Cohen RM, Murphy DL. The dexamethasone suppression test in patients with primary obsessive-compulsive disorder. Psychiatry Res. 1982;6:153–60.
pubmed: 6953457
doi: 10.1016/0165-1781(82)90003-8
Yehuda R, Southwick SM, Krystal JH, Bremner D, Charney DS, Mason JW. Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. Am J Psychiatry. 1993;150:83–86.
pubmed: 8417586
doi: 10.1176/ajp.150.1.83
Schreiber W, Lauer CJ, Krumrey K, Holsboer F, Krieg J-C. Dysregulation of the hypothalamic-pituitary-adrenocortical system in panic disorder. Neuropsychopharmacol. 1996;15:7–15.
doi: 10.1016/0893-133X(95)00146-5
Plotsky PM, Owens MJ, Nemeroff CB. PSYCHONEUROENDOCRINOLOGY OF DEPRESSION: Hypothalamic-Pituitary-Adrenal Axis. Psychiatr Clin North Am. 1998;21:293–307.
pubmed: 9670227
doi: 10.1016/S0193-953X(05)70006-X
Yehuda R. Current status of cortisol findings in post-traumatic stress disorder. Psychiatr Clin. 2002;25:341–68.
Yehuda R, Halligan SL, Golier JA, Grossman R, Bierer LM. Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder. Psychoneuroendocrinology 2004;29:389–404.
pubmed: 14644068
doi: 10.1016/S0306-4530(03)00052-0
Carpenter LL, Carvalho JP, Tyrka AR, Wier LM, Mello AF, Mello MF, et al. Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol Psychiatry. 2007;62:1080–7.
pubmed: 17662255
pmcid: 2094109
doi: 10.1016/j.biopsych.2007.05.002
de Kloet CS, Vermetten E, Heijnen CJ, Geuze E, Lentjes EGWM, Westenberg HGM. Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder. Psychoneuroendocrinology 2007;32:215–26.
pubmed: 17296270
doi: 10.1016/j.psyneuen.2006.12.009
Evanson NK, Tasker JG, Hill MN, Hillard CJ, Herman JP. Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling. Endocrinology 2010;151:4811–9.
pubmed: 20702575
pmcid: 2946139
doi: 10.1210/en.2010-0285
Jiang Z, Chen C, Weiss GL, Fu X, Stelly CE, Sweeten BLW, et al. Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice. Cell Rep. 2022;41:111509.
pubmed: 36261014
pmcid: 9635929
doi: 10.1016/j.celrep.2022.111509
Schmidt M, Levine S, Oitzl MS, van der Mark M, Müller MB, Holsboer F, et al. Glucocorticoid receptor blockade disinhibits pituitary-adrenal activity during the stress hyporesponsive period of the mouse. Endocrinology 2005;146:1458–64.
pubmed: 15591147
doi: 10.1210/en.2004-1042
Herman JP, Tasker JG. Paraventricular Hypothalamic Mechanisms of Chronic Stress Adaptation. Frontiers in Endocrinology. 2016;7:147.
Benham G. The Highly Sensitive Person: Stress and physical symptom reports. Personal Individ Diff. 2006;40:1433–40.
doi: 10.1016/j.paid.2005.11.021
Callahan ML, Storzbach D. Sensory sensitivity and posttraumatic stress disorder in blast exposed veterans with mild traumatic brain injury. Appl Neuropsychology: Adult. 2019;26:365–73.
doi: 10.1080/23279095.2018.1433179
van Marle HJF, Hermans EJ, Qin S, Fernández G. From specificity to sensitivity: how acute stress affects amygdala processing of biologically salient stimuli. Biol Psychiatry. 2009;66:649–55.
pubmed: 19596123
doi: 10.1016/j.biopsych.2009.05.014
Howerton AR, Roland AV, Fluharty JM, Marshall A, Chen A, Daniels D, et al. Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity. Biological Psychiatry. 2014. 2014. https://doi.org/10.1016/j.biopsych.2013.10.013 .
Homberg JR, Contet C. Deciphering the interaction of the corticotropin-releasing factor and serotonin brain systems in anxiety-related disorders. J Neurosci. 2009;29:13743–5.
pubmed: 19889985
pmcid: 2799301
doi: 10.1523/JNEUROSCI.4362-09.2009
Koegler-Muly SM, Owens MJ, Ervin GN, Kilts CD, Nemeroff CB. Potential corticotropin-releasing factor pathways in the rat brain as determined by bilateral electrolytic lesions of the central amygdaloid nucleus and the paraventricular nucleus of the hypothalamus. J Neuroendocrinol. 1993;5:95–98.
pubmed: 8485547
doi: 10.1111/j.1365-2826.1993.tb00367.x
Kalin NH, Fox AS, Kovner R, Riedel MK, Fekete EM, Roseboom PH, et al. Overexpressing corticotropin-releasing factor in the primate amygdala increases anxious temperament and alters its neural circuit. Biol Psychiatry. 2016;80:345–55.
pubmed: 27016385
pmcid: 4967405
doi: 10.1016/j.biopsych.2016.01.010
Swiergiel AH, Takahashi LK, Kalin NH. Attenuation of stress-induced behavior by antagonism of corticotropin-releasing factor receptors in the central amygdala in the rat. Brain Res. 1993;623:229–34.
pubmed: 8221104
doi: 10.1016/0006-8993(93)91432-R
Curtis AL, Bello NT, Connolly KR, Valentino RJ. Corticotropin-releasing factor neurones of the central nucleus of the amygdala mediate locus coeruleus activation by cardiovascular stress. J Neuroendocrinol. 2002;14:667–82.
pubmed: 12153469
doi: 10.1046/j.1365-2826.2002.00821.x
Adamec RE, McKay D. Amygdala kindling, anxiety, and corticotrophin releasing factor (CRF). Physiol Behav. 1993;54:423–31.
pubmed: 8415932
doi: 10.1016/0031-9384(93)90230-D
Sanford CA, Soden ME, Baird MA, Miller SM, Schulkin J, Palmiter RD, et al. A central amygdala CRF circuit facilitates learning about weak threats. Neuron 2017;93:164–78.
pubmed: 28017470
doi: 10.1016/j.neuron.2016.11.034
Tovote P, Fadok JP, Lüthi A. Neuronal circuits for fear and anxiety. Nat Rev Neurosci. 2015;16:317–31.
pubmed: 25991441
doi: 10.1038/nrn3945
Jo YS, Namboodiri VMK, Stuber GD, Zweifel LS. Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit. Nat Commun. 2020;11:422.
pubmed: 31969571
pmcid: 6976644
doi: 10.1038/s41467-020-14393-y
Hefner K, Whittle N, Juhasz J, Norcross M, Karlsson R-M, Saksida LM, et al. Impaired Fear Extinction Learning and Cortico-Amygdala Circuit Abnormalities in a Common Genetic Mouse Strain. J Neurosci. 2008;28:8074–85.
pubmed: 18685032
pmcid: 2547848
doi: 10.1523/JNEUROSCI.4904-07.2008
Brinks V, de Kloet ER, Oitzl MS. Corticosterone facilitates extinction of fear memory in BALB/c mice but strengthens cue related fear in C57BL/6 mice. Exp Neurol. 2009;216:375–82.
pubmed: 19162011
doi: 10.1016/j.expneurol.2008.12.011
Pattwell SS, Duhoux S, Hartley CA, Johnson DC, Jing D, Elliott MD, et al. Altered fear learning across development in both mouse and human. Proc Natl Acad Sci 2012;109:16318–23.
pubmed: 22988092
pmcid: 3479553
doi: 10.1073/pnas.1206834109
Riddle MC, McKenna MC, Yoon YJ, Pattwell SS, Santos PMG, Casey BJ, et al. Caloric restriction enhances fear extinction learning in mice. Neuropsychopharmacol. 2013;38:930–7.
doi: 10.1038/npp.2012.268
Xu Z, Adler A, Li H, Pérez-Cuesta LM, Lai B, Li W, et al. Fear conditioning and extinction induce opposing changes in dendritic spine remodeling and somatic activity of layer 5 pyramidal neurons in the mouse motor cortex. Sci Rep. 2019;9:4619.
pubmed: 30874589
pmcid: 6420657
doi: 10.1038/s41598-019-40549-y
Ramikie TS, Ressler KJ. Mechanisms of sex differences in fear and posttraumatic stress disorder. Biol Psychiatry. 2018;83:876–85.
pubmed: 29331353
doi: 10.1016/j.biopsych.2017.11.016
Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen C-Y, Choi KW, et al. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nat Commun. 2019;10:4558.
pubmed: 31594949
pmcid: 6783435
doi: 10.1038/s41467-019-12576-w
Tolin DF, Foa EB. Sex differences in trauma and posttraumatic stress disorder: a quantitative review of 25 years of research. Psychol Bull. 2006;132:959–92.
Garza K, Jovanovic T. Impact of gender on child and adolescent PTSD. Curr Psychiatry Rep. 2017;19:87.
pubmed: 28965303
doi: 10.1007/s11920-017-0830-6
Roeckner AR, Sogani S, Michopoulos V, Hinrichs R, van Rooij SJH, Rothbaum BO, et al. Sex-dependent risk factors for PTSD: a prospective structural MRI study. Neuropsychopharmacol. 2022;47:2213–20.
doi: 10.1038/s41386-022-01452-9
Becker JB, Monteggia LM, Perrot-Sinal TS, Romeo RD, Taylor JR, Yehuda R, et al. Stress and disease: is being female a predisposing factor? J Neurosci. 2007;27:11851–5.
pubmed: 17978023
pmcid: 6673348
doi: 10.1523/JNEUROSCI.3565-07.2007
Ravi M, Stevens JS, Michopoulos V. Neuroendocrine pathways underlying risk and resilience to PTSD in women. Front Neuroendocrinol. 2019;55:100790.
pubmed: 31542288
pmcid: 6876844
doi: 10.1016/j.yfrne.2019.100790
Walker CD, Tankosic P, Tilders FJ, Burlet A. Immunotargeted lesions of paraventricular CRF and AVP neurons in developing rats reveal the pattern of maturation of these systems and their functional importance. J Neuroendocrinol. 1997;9:25–41.
pubmed: 9023736
doi: 10.1046/j.1365-2826.1997.00544.x
Kolber BJ, Roberts MS, Howell MP, Wozniak DF, Sands MS, Muglia LJ. Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci 2008;105:12004–9.
pubmed: 18695245
pmcid: 2575312
doi: 10.1073/pnas.0803216105
Swanson LW, Sawchenko PE, Lind RW Regulation of multiple peptides in CRF parvocellular neurosecretory neurons: implications for the stress response. In: Hökfelt T, Fuxe K, Pernow B, editors. Progress in Brain Research, 68, Elsevier; 1986. p. 169-90.
Herman JP, Prewitt CM-F, Cullinan WE. Neuronal Circuit Regulation of the Hypothalamo-Pituitary-Adrenocortical Stress Axis. Crit Rev Neurobiol. 1996;10:371–94.
Gillies GE, Linton EA, Lowry PJ. Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature 1982;299:355–7.
pubmed: 6287293
doi: 10.1038/299355a0
Sawchenko PE, Swanson LW, Vale WW. Co-expression of corticotropin-releasing factor and vasopressin immunoreactivity in parvocellular neurosecretory neurons of the adrenalectomized rat. Proc Natl Acad Sci 1984;81:1883–7.
pubmed: 6369332
pmcid: 345027
doi: 10.1073/pnas.81.6.1883
Ma X-M, Lightman SL, Aguilera G. Vasopressin and corticotropin-releasing hormone gene responses to novel stress in rats adapted to repeated restraint. Endocrinology 1999;140:3623–32.
pubmed: 10433220
doi: 10.1210/endo.140.8.6943
Birnie MT, Short AK, de Carvalho GB, Taniguchi L, Gunn BG, Pham AL, et al. Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice. Nat Commun. 2023;14:1088.
pubmed: 36841826
pmcid: 9968307
doi: 10.1038/s41467-023-36780-x