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  2. Oxytocin antagonist induced visceral pain and corticotropin-releasing hormone neuronal activation in the central nucleus of the amygdala during colorectal distention in mice

Oxytocin antagonist induced visceral pain and corticotropin-releasing hormone neuronal activation in the central nucleus of the amygdala during colorectal distention in mice

  • Neurosci Res. 2021 Jul;168:41-53. doi: 10.1016/j.neures.2021.04.011.
Hiromichi Tsushima 1 Yanli Zhang 2 Tomohiko Muratsubaki 1 Motoyori Kanazawa 3 Shin Fukudo 4
Affiliations

Affiliations

  • 1 Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 2 Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China.
  • 3 Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan.
  • 4 Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan. Electronic address: sfukudo@med.tohoku.ac.jp.
Abstract

Activation of neurons containing oxytocin and corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus, the anterior cingulate cortex (ACC), and the central nucleus of the amygdala (CeA) during colorectal distention (CRD) is likely to play a crucial role in animal models of irritable bowel syndrome (IBS). Earlier studies in rodents showed that the microbiome is involved in social behavior via oxytocin expression in the brain. However, the detailed mechanism of visceral sensation and oxytocin is largely unknown. We tested the following hypotheses: (1) that oxytocin neurons in the PVN are activated by CRD, and (2) that the activation of oxytocin neurons by CRD is related to anxiety-like behavior, visceral perception, and an activation of CRH CeA neurons or ACC neurons. Oxytocin antagonist caused visceral hypersensitivity and anxiety-like behavior. In the PVN, oxytocin neurons were activated by CRD. Noxious CRD activated the CeA, basolateral nucleus of the amygdala (BLA), and ACC. High-dose oxytocin antagonist suppressed ACC activity and activated CRH CeA neurons. These results support our hypotheses. Oxytocin likely regulates CRH CeA neurons in an inhibitory manner and the ACC in an excitatory manner. Further research into the interaction of oxytocin and CRH in visceral pain and anxiety is warranted.

Keywords

Anterior cingulate cortex (ACC); Central nucleus of the amygdala (CeA); Colorectal distension; Corticotropin-releasing hormone (CRH); Oxytocin.

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