Injection of corticotropin‐releasing hormone into the amygdala aggravates visceral nociception and induces noradrenaline release in rats

• Published in: Neurogastroenterology and motility 2015-01, Vol.27 (1), p.30-39
• Main Authors: Su, J., Tanaka, Y., Muratsubaki, T., Kano, M., Kanazawa, M., Fukudo, S.
• Format: Article
• Language: English
• Subjects: Amygdala - drug effects; Amygdala - physiology; Animals; brain–gut interaction; central amygdaloid nucleus; Colon - pathology; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - physiology; CRD; Dilatation, Pathologic; Dopamine; Dopamine - secretion; Hormones; Male; Nociception - physiology; noradrenaline; Norepinephrine - secretion; Pyrimidines - pharmacology; Pyrroles - pharmacology; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Rectum - pathology; Rodents; serotonin; Serotonin - secretion
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12462

Background Corticotropin‐releasing hormone (CRH) and its receptor 1 (CRH‐R1) play an important role in the colonic response to stress. The central nucleus of the amygdala (CeA) is a major extrahypothalamic site that contains a large number of neurons expressing both CRH and CRH‐R1. Here, we verified the hypothesis that CRH in the CeA sensitizes visceral nociception via CRH‐R1 with release of noradrenaline, dopamine, and serotonin (5‐HT) in the CeA. Methods In male Wistar rats, visceral sensitivity was quantified by recording the visceromotor response to colorectal distension (CRD) with administration of vehicle, CRH, or the CRH‐R1 antagonist CP‐154526+ CRH or CRH‐R1 antagonist CP‐154526 alone into the CeA. Simultaneously, extracellular levels of noradrenaline, dopamine, and 5‐HT were measured in the CeA using microdialysis. All data were obtained under restraint conditions. Key Results Administration of CRH into the CeA significantly increased the number of abdominal muscle contractions in response to CRD. CP‐154526 significantly blocked the number of abdominal muscle contractions in response to CRD with the administration of CRH into the CeA. Noradrenaline in the CeA was increased by CRD, further increased by CRH, and inhibited by CRH‐R1 antagonist. Dopamine in the CeA was also exaggerated by CRH but was not inhibited by CRH‐R1 antagonist. 5‐HT in the CeA was unchanged. Conclusions & Inferences These results suggest that CRH in the CeA sensitizes visceral nociception via CRH‐R1 with release of noradrenaline. Corticotropin‐releasing hormone (CRH) and its receptor 1 (CRH‐R1) play an important role in the colonic response to stress. Here, we verified the hypothesis that CRH in the CeA sensitizes visceral nociception via CRH‐R1 with release of noradrenaline, dopamine, and serotonin (5‐HT) in the CeA. These results suggest that CRH in the CeA sensitizes visceral nociception via CRH‐R1 with release of noradrenaline.