Genetical and pharmacological inhibition of ATP-sensitive potassium channels induces anxiety-like behavior in mice

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  • Mochida Atsumi
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Miyagawa Kazuya
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Kimijima Hidenao
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Miyagishi Hiroko
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Kurokawa Kazuhiro
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Tsuji Minoru
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Umeda Akira
    Department of Respiratory Medicine, International University of Health and Welfare Shioya Hospital
  • Okada Yasumasa
    Department of Internal Medicine, National Hospital Organization Murayama Medical Center
  • Takeda Hiroshi
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare

Bibliographic Information

Other Title
  • K<sub>ATP</sub>チャネルの遺伝的および薬理学的阻害はマウスの不安様行動を誘発する

Description

<p>Although Kir6.2, one of the subunits composed ATP-sensitive potassium (KATP) channels, are widely distributed in the brain, the roles in emotional behavior are not yet fully understood. Here we investigated the behavioral characteristics of Kir6.2-deficient (Kir6.2-/-) mice. Kir6.2-/- mice showed anxiety-like behavior in the elevated-plus maze test and light-dark test, especially, it was prominent in females. Immunohistochemical studies showed that Kir6.2 was co-localized with tryptophan hydroxylase (TPH) in the dorsal raphe nuclei and tyrosine hydroxylase (TH) in the ventral tegmental area/locus coeruleus. Interestingly, TPH expression in the midbrain was significantly elevated in female Kir6.2-/- mice. These results suggest that Kir6.2 expressed in serotonergic neurons could play a key role in emotional behavior. Furthermore, we investigated whether pharmacological blockade of KATP channels affects the emotional behavior. Mice that had been injected intracerebroventricularly with glibenclamide, a selective KATP channel blocker, showed anxiety-like behavior in the elevated-plus maze test. These results confirm a critical role of KATP channels in regulation of emotional behavior.</p>

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