A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF(1) receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo[1,5-a]pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF(1) antagonists with lower lipophilicity.
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Targeting corticotropin-releasing hormone receptor type 1 (Crhr1) neurons: validating the specificity of a novel transgenic Crhr1-FlpO mouse.
Brain Struct Funct
December 2024
Brown Foundation Institute of Molecular Medicine of McGovern Medical School, University of Texas Health Sciences Center-Houston, Houston, TX, USA.
Corticotropin-releasing hormone (CRH) signaling through its cognate receptors, CRHR1 and CRHR2, contributes to diverse stress-related functions in the mammalian brain. Whereas CRHR2 is predominantly expressed in choroid plexus and blood vessels, CRHR1 is abundantly expressed in neurons in discrete brain regions, including the neocortex, hippocampus and nucleus accumbens. Activation of CRHR1 influences motivated behaviors, emotional states, and learning and memory.
View Article and Find Full Text PDFIncreased CRF-R1 transmission in the nucleus accumbens shell facilitates maternal neglect in lactating rats and mediates anxiety-like behaviour in a sex-specific manner.
Neuropharmacology
March 2025
Department of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of Regensburg, Regensburg, Germany. Electronic address:
During the transition to motherhood, complex brain adaptations occur to ensure adequate maternal responses to offspring' needs accompanied by reduced anxiety. Among others, the corticotropin-releasing factor (CRF) and oxytocin (OXT) systems have emerged as crucial regulators of these essential postpartum adaptations. Here, we investigated their roles within the nucleus accumbens shell (NAcSh), a central region of the reward and maternal circuits, in maternal neglect of lactating rats.
View Article and Find Full Text PDFRegion-specific neuroadaptations of CRF1 and CRF2 expression following heroin exposure in female rats.
Pharmacol Biochem Behav
December 2024
Department of Psychological and Brain Sciences, Colgate University, Hamilton, NY, USA. Electronic address:
Article Synopsis
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4-Methoxycinnamic acid ameliorates post-traumatic stress disorder-like behavior in mice by antagonizing the CRF type 1 receptor.
Life Sci
January 2025
Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address:
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The effects of corticotropin-releasing factor (CRF) and urocortins on the noradrenaline (NA) released from the locus coeruleus (LC).
Peptides
December 2024
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates the noradrenergic neurotransmission, both processes being implicated in the pathogenesis of anxiety and depression, but the intimate site and mechanism of interaction of CRF and CRF-related peptides, named urocortins (UCN1, UCN2, UCN3), with noradrenaline (NA) was not fully elucidated yet. Therefore, the aim of the present study was to investigate the actions of CRF and urocortins on the NA released from the rat locus coeruleus (LC), the primary source of NA in the brain, and the participation of CRF receptors (CRF1 and CRF2) in these actions. In order to do so, male Wistar rats were used, their LC were isolated and dissected, and the LC slices were incubated with tritium-labelled NA, superfused and stimulated electrically.
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