Cited by 241Stress Responses and CortisolRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

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Ghrelin Regulates the Hypothalamic-Pituitary-Adrenal Axis and Restricts Anxiety After Acute Stress

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Spencer, Sarah J., Xu, Lu, Clarke, Melanie A., Lemus, Moyra, Reichenbach, Alex, Geenen, Bram, Kozicz, Tamás, Andrews, Zane B.·2012·Biological Psychiatry

DOI 10.1016/j.biopsych.2012.03.010

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Abstract

Background Ghrelin plays important roles in glucose metabolism, appetite, and body weight regulation, and recent evidence suggests ghrelin prevents excessive anxiety under conditions of chronic stress.Methods We used ghrelin knockout (ghr-/-) mice to examine the role of endogenous ghrelin in anxious behavior and hypothalamic-pituitary-adrenal axis (HPA) responses to acute stress.Results Ghr-/- mice are more anxious after acute restraint stress, compared with wild-type (WT) mice, with three independent behavioral tests. Acute restraint stress exacerbated neuronal activation in the hypothalamic paraventricular nucleus and medial nucleus of the amygdala in ghr-/- mice compared with WT, and exogenous ghrelin reversed this effect. Acute stress increased neuronal activation in the centrally projecting Edinger-Westphal nucleus in WT but not ghr-/- mice. Ghr-/- mice exhibited a lower corticosterone response after stress, suggesting dysfunctional glucocorticoid negative feedback in the absence of ghrelin. We found no differences in dexamethasone-induced Fos expression between ghr-/- and WT mice, suggesting central feedback was not impaired. Adrenocorticotropic hormone replacement elevated plasma corticosterone in ghr-/-, compared with WT mice, indicating increased adrenal sensitivity. The adrenocorticotropic hormone response to acute stress was significantly reduced in ghr-/- mice, compared with control subjects. Pro-opiomelanocortin anterior pituitary cells express significant growth hormone secretagogue receptor.Conclusions Ghrelin reduces anxiety after acute stress by stimulating the HPA axis at the level of the anterior pituitary. A novel neuronal growth hormone secretagogue receptor circuit involving urocortin 1 neurons in the centrally projecting Edinger-Westphal nucleus promotes an appropriate stress response. Thus, ghrelin regulates acute stress and offers potential therapeutic efficacy in human mood and stress disorders.

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Ghrelin signalling in AgRP neurons links metabolic state to the sensory regulation of AgRP neural activity
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“In many cases the actions of ghrelin phenocopy those of AgRP neurons; 1) ghrelin is a bona fide hunger signal as ghrelin injection to ad libitum fed mice elicits an operant behavioural response learned during hunger (fasting) [6; 36]; 2) ghrelin increases food intake, motivation and dopamine neural circuits [22; 37-39…”
Background
Ghrelin but not nesfatin-1 affects certain forms of learning and memory in both rats and mice
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“Ghrelin has been shown to regulate a variety of biological/behavioral processes, including (but not limited to) cell proliferation and apoptosis, energy balance, survival, glucose metabolism, gastrointestinal motility, sexual behavior, learning and memory, neuroprotection, stress response, and reward processing (Bali…”
Effects of exogenous ghrelin administration and ghrelin receptor blockade, in combination with alcohol, on peripheral inflammatory markers in heavy-drinking individuals: Results from two human laboratory studies
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“Ghr-R KO mice show increased anxiety and depression when subjected to stress [49,54], highlighting the potential role of ghrelin as a defender against the negative effects of stress.”
Background
Ghrelin and leptin levels in children with anxiety disorders
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Diet and companionship modulate pain via a serotonergic mechanism
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Acylated Ghrelin Supports the Ovarian Transcriptome and Follicles in the Mouse: Implications for Fertility
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“Researchers have suggested that anxiety disorders impair the regular functions of the hypothalamic-pituitary-adrenal (HPA) axis, causing an increase in appetite [76] due to alterations in the two hormones, ghrelin and leptin.”
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“Ghrelin was indeed shown to alleviate stress-induced anxiety and may also exert antidepressive-like effects when injected to rodents (17, 18).”
Background
Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study
Farokhnia, M., Abshire, K. M., Hammer, A., Deschaine, S. L., Saravanakumar, A., Cobbina, E., You, Z., Haass‐Koffler, C. L., Lee, M. R., Akhlaghi, F., et al. (2021) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyab004 · Cited by 19
A possible role for ghrelin, leptin, brain-derived neurotrophic factor and docosahexaenoic acid in reducing the quality of life of coeliac disease patients following a gluten-free diet
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“Its potential action as a stress-feedback signal that regulates a diverse number of functions, including stress responses and mood, has gained increasing interest [16], but data in the literature are still inconclusive.”
Background
Chronic predator stress in female mice reduces primordial follicle numbers: implications for the role of ghrelin
Natale, M. R. D., Soch, A., Ziko, I., Luca, S. N. D., Spencer, S. J., & Sominsky, L. (2019) · Journal of Endocrinology · doi:10.1530/joe-19-0109 · Cited by 16
Effects of disrupted ghrelin receptor function on fear processing, anxiety and saccharin preference in mice
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Ghrelin, Neuroinflammation, Oxidative Stress, and Mood Disorders: What Are the Connections?
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“regulating anterior pituitary release of ACTH), an effect which also impacts on anxiety-like behaviors [Spencer et al. 2012].”
Background
Elevated serum ghrelin, tumor necrosis factor‐α and interleukin‐6 in congenital heart disease
Wang, D., Fang, J. C., Wang, R.-G., Sun, D., Xia, K., Yin, W., Zhang, S., & Sun, L. (2015) · Pediatrics International · doi:10.1111/ped.12773 · Cited by 16
Gray areas: Neuropeptide circuits linking the Edinger-Westphal and Dorsal Raphe nuclei in addiction
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Association Between Self-rating Depression Scores and Total Ghrelin and Adipokine Serum Levels in a Large Population-Based Sample
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“chronic stress exposure (6, 57–59), feeding state (60) and whether animals were stressed or unstressed previous to ghrelin exposure (57).”
Background
Lower Ghrelin Levels Are Associated With Higher Anxiety Symptoms in Adolescents and Young Adults With Avoidant/Restrictive Food Intake Disorder
Sella, A. C., Hadaway, N. A., Stern, C. M., Becker, K. R., Holsen, L. M., Eddy, K. T., Micali, N., Misra, M., Thomas, J. J., & Lawson, E. A. (2023) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.22m14482 · Cited by 15
Hunger signalling in the olfactory bulb primes exploration, food-seeking and peripheral metabolism
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“Interestingly, ghrelin and GHSR function are also linked with reduced anxiety-like and depressive-like behavior [64 e 67], including following olfactory bulbectomy in mice [68], although the main sites of action have not been fully elucidated.”
Background
Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response
Sominsky, L., Ziko, I., & Spencer, S. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173498 · Cited by 15
Serum ghrelin is positively associated with physiological anxiety but negatively associated with pathological anxiety in humans: Data from a large community-based study
Wittekind, D. A., Kratzsch, J., Mergl, R., Riedel-Heller, S. G., Witte, A. V., Villringer, A., & Kluge, M. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105728 · Cited by 15
Cognitive effects of acute restraint stress in male albino rats and the impact of pretreatment with quetiapine versus ghrelin
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Acylated ghrelin suppresses the cytokine response to lipopolysaccharide and does so independently of the hypothalamic-pituitary-adrenal axis
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Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation
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Ghrelin‐related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries
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“Acylated ghrelin is a potent agonist at the growth hormone secretagogue receptor 1a (GHSR1a), which is the only functional ghrelin receptor identified to date.(5,6)”
Background
Relationship between Orexigenic Peptide Ghrelin Signal, Gender Difference and Disease
Yamada, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073763 · Cited by 15
“expressed in the hypothalamic nucleus [14,15] and is also localized in the ventral tegmental area (VTA) [16], amygdala [17], and hippocampus [18].”
Background
Ghrelin mediated regulation of neurosynaptic transmitters in depressive disorders
Masule, M. V., Rathod, S., Agrawal, Y. O., Patil, C. R., Nakhate, K. T., Ojha, S. K., Goyal, S. N., & Mahajan, U. B. (2022) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2022.100113 · Cited by 15
“The concept that ghrelin has a dual impact, that it may be anxiogenic or anxiolytic depending on the conditions, might explain some but not all the contradictory evidence (Meyer et al., 2014; Spencer et al., 2012).”
Result
Gender Differences in Ghrelin Response to Chronic Immobilization Stress in Rats: Possible Role of Estrogen
Elbassuoni, E. (2013) · General Physiology and Biophysics · doi:10.4149/gpb_2013061 · Cited by 14
Manual Acupuncture at PC6 Ameliorates Acute Restraint Stress‐Induced Anxiety in Rats by Normalizing Amygdaloid Noradrenergic Response
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“In rats, ARS increases plasma corticosterone (CORT) levels [1] and causes an imbalance in the hippocampal redox state [2].”
Background
Ghrelin-reactive immunoglobulins and anxiety, depression and stress-induced cortisol response in adolescents. The TRAILS study
François, M., Schaefer, J. M., Bôle‐Feysot, C., Déchelotte, P., Verhulst, F. C., & Fetissov, S. O. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.12.011 · Cited by 13
“, 2008) and under stress conditions, endogenous ghrelin seems to attenuate anxious-like behavior and hypothalamic–pituitary–adrenal (HPA) axis activation (Spencer et al., 2012).”
Influential
Reduction in total plasma ghrelin levels following catecholamine depletion: Relation to bulimic and depressive symptoms
Homan, P., Grob, S., Milos, G. F., Schnyder, U., & Hasler, G. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.12.024 · Cited by 13
“Furthermore, it has been proposed that ghrelin reduces stress-induced anxiety by stimulating the HPA axis at the anterior pituitary (Spencer et al., 2012).”
Background
Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus
Füredi, N., Nagy, Á., Mikó, A., Berta, G., Kozicz, T., Pétervári, E., Balaskó, M., & Gaszner, B. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.03.002 · Cited by 13
Targeting the Ghrelin Receptor as a Novel Therapeutic Option for Epilepsy
Buckinx, A., Bundel, D. D., Kooijman, R., & Smolders, I. J. (2021) · Biomedicines · doi:10.3390/biomedicines10010053 · Cited by 16
“Additionally, ghrelin confers a regulatory role on growth hormone (GH) release [19], is implicated in learning and memory [21–23], modulates motivation and reward [24,25], and regulates the stress response (reviewed in [26]).”
Background
The role of ghrelin/GHS-R1A signaling in nonalcohol drug addictions
Sustkova-Fiserova, M., Charalambous, C., Khryakova, A., Certilina, A., Lapka, M., & Šlamberová, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020761 · Cited by 12
Role of aldosterone and mineralocorticoid receptor (MR) in addiction: A scoping review
Pince, C. L., Whiting, K. E., Wang, T., Lékó, A. H., Farinelli, L. A., Cooper, D., Farokhnia, M., Vendruscolo, L. F., & Leggio, L. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105427 · Cited by 12
Midbrain raphe 5-HT 1A receptor activation alters the effects of ghrelin on appetite and performance in the elevated plus maze
Wauson, S. E. R., Sarkodie, K., Schuette, L. M., & Currie, P. J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115581981 · Cited by 12
“It is also in agreement with recent evidence suggesting that ghrelin reduces anxiety after acute stress by stimulating the hypothalamic–pituitary–adrenal axis via the anterior pituitary (Spencer et al., 2012).”
Result
Food‐Restriction Lowers the Acoustic Startle Response in both Male and Female Rats, and, in Combination with Acute Ghrelin Injection, Abolishes the Expression of Fear‐Potentiated Startle in Male Rats
Toufexis, D. J., Lipatova, O., Johnson, A. C., & Abizaid, A. B. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12436 · Cited by 12
Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin
Polishchuk, H., Guzik, K., & Kantyka, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262210996 · Cited by 16
“It has been reported that ghrelin administration increases cortisol and growth hormone (GH), with only a weak trend toward mood improvement in male patients [270], and that ghrelin can alleviate anxiety after short-term stress by activating the HPA axis [271].”
Novel Regulator of Acylated Ghrelin, CF801, Reduces Weight Gain, Rebound Feeding after a Fast, and Adiposity in Mice
Wellman, M. K., Patterson, Z. R., MacKay, H., Darling, J. E., Mani, B. K., Zigman, J. M., Hougland, J. L., & Abizaid, A. B. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00144 · Cited by 11
The Gut–Brain-Axis as a Target to Treat Stress-Induced Obesity
Lee, C. Y., & Abizaid, A. B. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00117 · Cited by 11
“Nevertheless, enthusiasm for these types of drugs has been hampered by evidence suggesting that stress-induced ghrelin secretion is necessary not only to maintain metabolic homeostasis but also to prevent stress-induced depressive like behaviors and reduce anxiety (28, 53, 54).”
Background
Ghrelin and depressive symptoms in patients with first‐episode drug‐naïve major depressive disorder: The mediating role of hypothalamic‐pituitary‐adrenal axis
Zhang, C., Dong, Y., Li, S., Li, M., Gao, Y., Liu, Y. S., Liu, X., Zhou, C., & Li, J. (2024) · Asia-Pacific Psychiatry · doi:10.1111/appy.12552 · Cited by 10
“This effect has also been found in animal models of chronic unpredictable mild stress (CUMS) (Spencer et al., 2012).”
Background
To eat or not to eat: A role for ghrelin and LEAP2 in eating disorders?
Tolle, V., du Montcel, C. T., Mattioni, J., Schéle, E., Viltart, O., & Dickson, S. L. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104045 · Cited by 11
“Stress exposure in rodents increases ghrelin levels (Asakawa et al., 2001; Kristenssson et al., 2006; Lutter et al., 2008; Patterson et al., 2010; Spencer et al., 2012), and conversely, ghrelin administration has been shown to activate the hypothalamo-pituitary-adrenal (HPA) stress axis, raising…”
GHSR blockade, but not reduction of peripherally circulating ghrelin via β1-adrenergic receptor antagonism, decreases binge-like alcohol drinking in mice
Richardson, R. S., Kryszak, L. A., Vendruscolo, J. C. M., Koob, G. F., Vendruscolo, L. F., & Leggio, L. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02713-3 · Cited by 10
Does Stress Elicit Depression? Evidence From Clinical and Preclinical Studies
Sickmann, H. M., Li, Y., Mørk, A., Sánchez, C., & Gulinello, M. E. (2014) · Current topics in behavioral neurosciences · doi:10.1007/7854_2014_292 · Cited by 10
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Ghrelin receptor signaling is not required for glucocorticoid-induced obesity in female mice
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Elevated ghrelin alters the behavioral effects of perinatal acetaminophen exposure in rats
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Orexinergic innervation of urocortin1 and cocaine and amphetamine regulated transcript neurons in the midbrain centrally projecting Edinger–Westphal nucleus
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“…stress response (Kuru et al., 2000; Al-Barazanji et al., 2001; Sakamoto et al., 2004), similarly to that of EWcp-Ucn1 neurons (Kozicz et al., 2001, 2011a,b; Kozicz, 2003, 2007; Gaszner et al., 2004; Linden et al., 2004; Cunha et al., 2007; Xu et al., 2009; Okere et al., 2010; Spencer et al., 2012).”
BackgroundInfluential
Impact of [d-Lys3]-GHRP-6 and feeding status on hypothalamic ghrelin-induced stress activation
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“Moreover, a study has revealed that ghrelin can alleviate anxiety following short-term stress by activating the HPA axis [35].”
Influential
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Pearl, A. J., Maddern, X. J., Pinares-Garcia, P., Ursich, L. T., Anversa, R. G., Shesham, A., Brown, R. M., Reed, F. M., Giardino, W. J., Lawrence, A. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57880-w · Cited by 9
“Our ﬁ ndings differ from previous reports in Ghsr -GFP reporter mice suggesting expression overlapped >90% with the peptidergic marker Ucn1 23 ; however, this may be due to incomplete reporter expression, or expression levels required to drive recombination and reporter expression in a transgenic…”
Influential
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“Stress-related food intake change is mediated by ghrelin (Chuang et al., 2011), potentially through an interaction between ghrelin and the HPA axis (Spencer et al., 2012, 2015).”
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de Paula, D. E., Vilela, F. C., & Giusti‐Paiva, A. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120173 · Cited by 7
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“The significant impact of ghrelin on the hypothalamic–pituitary–adrenal axis has been documented in numerous reports and reviews (Spencer et al.”
Background
Nucleus accumbens ghrelin signaling controls anxiety-like behavioral response to acute stress
Chang, L., He, Y., Tian, T., & Li, B. (2024) · Behavioral and Brain Functions · doi:10.1186/s12993-024-00244-z · Cited by 5
“In line with this, ghrelin knockout mice display more anxious after acute restraint stress, compared with wild-type mice [5].”
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Central Amygdala Neuroplasticity in Alcohol Dependence
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Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice
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“1 is not clear on when animals were sacrificed relative to the final measurement of EPM (or when EPM was conducted relative to the final restraint session).”
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Örüm, D., Korkmaz, S., İlhan, N., Örüm, M. H., & Atmaca, M. (2024) · Psychiatry Investigation · doi:10.30773/pi.2023.0309 · Cited by 4
“34,38 Studies suggesting that ghrelin has an anxiolytic effect include peripheral ghrelin administration, 35 while studies suggesting an anxiogenic effect include central ghrelin administration.”
Background
Ghrelin in Depression: A Promising Therapeutic Target
Kore, M. S., Mamsa, R., Patil, D., & Bhatt, L. K. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04554-1 · Cited by 4
“After persistent social defeat stress or acute restraint stress, GHSR and ghrelin null mice have considerably lower plasma corticosterone concentrations and exhibit more anxiety-like behavior [95, 97].”
Role of dorsal raphe nucleus GHS-R1a receptors in the regulation of inhibitory avoidance and escape behaviors in rats
Cavalcante, D. P., Turones, L. C., Camargo-Silva, G., Santana, J. S., Colugnati, D. B., Pansani, A. P., Xavier, C. H., & Pobbe, R. L. H. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.03.017 · Cited by 4
“[25] used ghrelin knockout mice to assess the role of endogenous ghrelin in anxious behavior and hypothalamic-pituitary-adrenal axis (HPA) responses to acute stress.”
Day/night Changes in the Dorsomedial Hypothalamus Firing Responses to Ghrelin are Modulated by High-fat Diet
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Impaired Ghrelin Signaling Does Not Lead to Alterations of Anxiety-like Behaviors in Adult Mice Chronically Exposed to THC during Adolescence
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“GHSR and ghrelin knockout mice showed decreased plasma levels of corticosterone after chronic social defeat stress and acute restraint stress, as well as increased anxiety-like behavior [32,33].”
Background
Longitudinal changes of associations between the preproghrelin Leu72Met polymorphism with depression in Chinese Han adolescents after the Wenchuan earthquake
Su, M., Cao, T., Feng, Y., Guo, Q., Fan, M., & Fang, D. Z. (2017) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000180 · Cited by 4
“Furthermore, recent evidences suggest that ghrelin may play an important role in regulating the hypothalamic–pituitary–adrenal (HPA) stress axis with exposures of stressors (Lutter et al., 2008; Spencer et al., 2012; Patterson et al., 2013).”
Background
Post-bariatric surgery quality-of-life decline: analysis of the gut–brain axis
Jiao, Y., Zhu, S., Xue, H., Wang, Y., Wang, Y., & Hou, D. (2025) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-025-01784-7 · Cited by 3
“However, in ghrelin gene knockout mouse models, anxiety effects under acute stress are enhanced, while anxiety-like behaviors are reduced under non-stress conditions [28].”
Childhood sexual abuse is associated with higher total ghrelin serum levels in adulthood: results from a large, population-based study
Wittekind, D. A., Kratzsch, J., Mergl, R., Wirkner, K., Baber, R., Sander, C., Witte, A. V., Villringer, A., & Kluge, M. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02517-z · Cited by 3
Evidence for independent actions of the CRF and ghrelin systems in binge-like alcohol drinking in mice
Richardson, R. S., Kryszak, L. A., Vendruscolo, J. C. M., Koob, G. F., Leggio, L., & Vendruscolo, L. F. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111341 · Cited by 3
Blockade of Ghrelin Receptor Signaling Enhances Conditioned Passive Avoidance and Context-Associated cFos Activation in Fasted Male Rats
Edwards, C. M., Guerrero, I. E., Dolezel, T., Zheng, H., & Rinaman, L. (2022) · Neuroendocrinology · doi:10.1159/000528828 · Cited by 3
GHS-R1a signaling drives anxiety-related behavior by shaping excitability of ventromedial hypothalamic neurons
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The Role of the Ghrelin Receptor in Appetite and Energy Metabolism
Stark, R., & Andrews, Z. B. (2014) · The Receptors · doi:10.1007/978-1-4939-0823-3_3 · Cited by 2
Ghrelin Plays a Role in Various Physiological and Pathophysiological Brain Functions
Spencer, S. J. (2014) · The Receptors · doi:10.1007/978-1-4939-0823-3_12 · Cited by 2
Acute iv CRH administration significantly increases serum active ghrelin in postmenopausal PCOS women compared to postmenopausal controls
Markopoulos, M. C., Barber, T. M., Bargiota, Α., Skevaki, C. L., Papassotiriou, I., Kumar, S., Vlahos, N., Mastorakos, G. P., & Valsamakis, G. (2023) · Endocrine · doi:10.1007/s12020-023-03406-7 · Cited by 2
“The enhanced secretion of ghrelin following exogenous CRH administration (a pathophysiologic consequence of acute stress), in PCOS postmenopausal women might be explained by previously described mechanisms [37, 48], in which acute stimulation of the HPA axis enhances ghrelin secretion and subsequent diminishment of an…”
Neurobiology of Avoidant/Restrictive Food Intake Disorder
Scharner, S. (2024) · Psychiatric Annals · doi:10.3928/00485713-20240117-02 · Cited by 3
Peri-adolescent THC exposure does not lead to anxiety-like behavior in adult micePreprint
Šestan-Peša, M., Shanabrough, M., Horváth, T. L., & Miletta, M. C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.31.274274 · Cited by 2
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Background
Blockade of ghrelin receptor signaling enhances conditioned passive avoidance and context-associated neural circuit activation in fasted male ratsPreprint
Edwards, C. M., Guerrero, I. E., Dolezel, T., Zheng, H., & Rinaman, L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.11.480168 · Cited by 2
“Further, caloric restriction reduces innate avoidance behavior in wildtype mice but not in mice lacking ghrelin receptors (Lutter et al., 2008), which display more innate anxiety-like behavior than wildtype mice (Spencer et al., 2012).”
Background

Authors: Spencer, S. J., Xu, L., Clarke, M. A., Lemus, M., Reichenbach, A., Geenen, B., Kozicz, T., & Andrews, Z. B.
Affiliations: Monash University (AU)
Radboud University Nijmegen (NL)
Corresponding author: Andrews, Zane B.
ORCID: Spencer, Sarah J.
Xu, Lu
Reichenbach, Alex
Geenen, Bram
Kozicz, Tamás
Andrews, Zane B.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2012-09
Volume: 72
Issue: 6
Pages: 457-465
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2012.03.010
OpenAlex: W2068804599
Cited by: 241
References: 54
Citations by year: 2026: 9 · 2025: 10 · 2024: 23 · 2023: 11 · 2022: 15 · 2021: 20 · 2020: 15 · 2019: 16 · 2018: 13 · 2017: 23 · 2016: 22 · 2015: 16 · 2014: 21 · 2013: 22 · 2012: 4
FWCI: 8.36
Type: journal article
Language: en
Open access: green
figshare.com
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
RMIT Research Repository (RMIT University Library) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: National Health and Medical Research Council of Australia (1011274)
Australian Research Council (DP109339)
Monash Fellowship (FT100100966)
National Health and Medical Research Council Peter Doherty Research Fellowship (465167)
Endocrine Society of Australia Postdoctoral Fellowship (FT110100084)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: ghrelin, hypothalamic-pituitary-adrenal axis, anxiety, acute stress, restraint stress, corticosterone, glucocorticoid negative feedback, ACTH, anterior pituitary, growth hormone secretagogue receptor, proopiomelanocortin, Edinger-Westphal nucleus, urocortin 1, paraventricular nucleus, amygdala, stress response
MeSH terms: Adrenocorticotropic Hormone, Analysis of Variance, Animals, Anxiety, Corticosterone, Corticotropin-Releasing Hormone, Dexamethasone, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Restraint, Physical, Stress, Psychological, Mice, Knockout, Mice, Ghrelin, Receptors, Ghrelin

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Ghrelin Regulates the Hypothalamic-Pituitary-Adrenal Axis and Restricts Anxiety After Acute Stress

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