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Corticotropin-releasing factor (CRF) processes in acute and chronic anxiety
Published in Philip N. Murphy, The Routledge International Handbook of Psychobiology, 2018
Paula S. M. Yamashita, James E. Hassell, Christopher A. Lowry
Antalarmin is widely used in preclinical studies as a selective CRFR1 antagonist, and it has been successfully tested in rhesus monkeys. This antagonist could reduce the stress-induced increase in the CSF CRF levels, suppress anxiety- and fear-related responses, and increase exploratory and sexual behavior during a stressful situation (Habib et al., 2000).
Beyond Homeostasis
Published in Ruth B.S. Harris, Appetite and Food Intake, 2017
Mark E. Wilson, Vasiliki Michopoulos
Because reduced glucocorticoid negative feedback as a consequence of chronic exposure to stressors is characterized by an up-regulation of central CRF signaling (Dallman et al. 2004, Herman 2013), the use of CRF receptor antagonists could provide insights into the role of this neuropeptide in sustaining excessive palatable food consumption. Acute administration of a CRF type 1–2 receptor antagonist, which is unable to penetrate the blood–brain barrier, does not reduce this emotional feeding phenotype shown by subordinates in a choice dietary environment despite a significant reduction in serum cortisol (Michopoulos et al. 2010). However, different results are observed with the use of the CRF type 1 receptor antagonist, antalarmin, which does penetrate the brain when administered peripherally (Moore et al. 2014). During vehicle treatments, subordinate females consume significantly more calories in a dietary environment that includes a choice between a chow diet and a high-caloric diet than do dominant females. Two days of peripheral administration of antalarmin significantly reduces daily caloric intake in subordinate female monkeys to amounts comparable to those consumed by dominant group mates in the choice dietary environment (Moore et al. 2014). Moreover, examination of agonistic behaviors that define rank indicate that the animals that exhibited higher rates of submissive behaviors, most typically the more subordinate animals responding to aggression from group mates, and those animals that were the most aggressive were significantly more sensitive to the attenuation in emotional feeding by antalarmin (Moore et al. 2014). While one would expect dominant animals to be more aggressive to enforce their social status on lower ranking females (Bernstein 1976), the absolute frequency of aggression is unrelated to specific dominance ranks (Bernstein, Gordon, and Rose 1974) and may thus reflect a female’s reaction to her social environment. This hypothesis is consistent with the notion that increased aggression, as a form of defensive behavior, may be a consequence of an animal’s adaptation to its position is a social hierarchy (Honess and Marin 2006). While depression or behavioral inhibition may be an outcome of chronic stressor exposure (Nemeroff and Vale 2005), data from diverse species indicate that CRF increases social aggression (Tazi et al. 1987, Robison et al. 2004, Backstrom and Winberg 2013). Thus, it seems likely that increased rates of submission, typical of more subordinate animals, and aggression, most typical of more dominant monkeys, are behavioral manifestations of the socially induced stress in the context of a female macaque dominance hierarchy. This analysis highlights the role of a female’s response to the social environment in the appetite suppressing effects of CRF1 receptor antagonist in this rich dietary environment.
The effect of a corticotropin-releasing factor receptor 1 antagonist on the fear conditioning response in low- and high-anxiety rats after chronic corticosterone administration
Published in Stress, 2019
Anna Skórzewska, Aleksandra Wisłowska-Stanek, Małgorzata Lehner, Danuta Turzyńska, Alicja Sobolewska, Paweł Krząścik, Janusz Szyndler, Piotr Maciejak, Adam Płaźnik
We have found that HR rats treated with corticosterone exhibited an increase in freezing duration in comparison with the appropriate control group and the treated LR group. In the HR group, the behavioral effect was accompanied by a decrease in the number of GR-immunoreactive nuclei in the IL, DG and CA3 area of hippocampus in comparison with the appropriate control group and the treated LR group, and by an increase in the number of GR-positive nuclei in the basal amygdala (BA) in comparison with that in the control group. Moreover, in the HR group treated with corticosterone, the number of CRF-immunoreactive cells in the pPVN and CA1 area of hippocampus was decreased in comparison with the appropriate control group and the treated LR group, and in the DG in comparison with the control group. Antalarmin administration significantly attenuated the conditioned fear responses, increased plasma corticosterone concentration, and decreased number of GR-immunoreactive nuclei in the BA in the HRcort group only. Additionally, in this group of rats, the CRF1 receptor antagonist significantly reduced the effect of corticosterone on the number of GR-immunoreactive nuclei in the IL, DG and CA3 area of hippocampus, and number of CRF-immunoreactive cells in the pPVN, DG, and CA1 area of the hippocampus.
Advances in the available non-biological pharmacotherapy prevention and treatment of acute mountain sickness and high altitude cerebral and pulmonary oedema
Published in Expert Opinion on Pharmacotherapy, 2018
K.E. Joyce, S.J.E. Lucas, C.H.E. Imray, G.M Balanos, A. D. Wright
CP154,526 is a CRHR1 antagonist, negating the effects of CRH. CP154,526 appears to reduce the hypoxia-associated increases in pro-inflammatory markers, such as TNF-α and IL-1β, which correlate AMS [161]. It is possible that CP154,526 may reduce the stress response associated with hypoxia and reduce the incidence of AMS. Future research is warranted for the efficacy in altitude illness of CRHR1 antagonists such as antalarmin and pexacerfont in addition to CP154,526.