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論文
- タイトル
- タイトル（英）
- Cannabinoid CB2 receptors and hypersensitivity to methamphetamine: Vulnerability to schizophrenia.
- 参照URL
- https://researchmap.jp/yhoriuchi/published_papers/44353271
- 著者
- 著者（英）
- Ana Canseco-Alba,Koichi Tabata,Momoki Yukihiko,Taharima Tabassum,Yasue Horiuchi,Tadao Arinami,Emmanuel S Onaivi,Hiroki Ishiguro
- 担当区分
- 概要
- 概要（英）
- The human cannabinoid receptor 2 (CB2R) gene CNR2 has been associated with schizophrenia development. Inbred mice treated with the CB2R inverse agonist AM630 and challenged with methamphetamine (MAP) showed reduced prepulse inhibition (%PPI) response and locomotor hyperactivity, both behavioral measures in rodents that correlate with psychosis. Mice lacking CB2R on striatal dopaminergic neurons exhibit a hyperdopaminergic tone and a hyperactivity phenotype. Hyperdopaminergia plays a role in the etiology of schizophrenia. This study aimed to determine the direct role of CB2R, heterozygous Cnr2 gene knockout (Het) mice treated with MAP to induce behavioral sensitivity mimicking a schizophrenia-like human phenotype. Additionally, the study aims to explore the unique modulation of dopamine activity by neuronal CB2R. Conditional knockout DAT-Cnr2-/- mice were evaluated in response to MAP treatments for this purpose. Sensorimotor gating deficits in DAT-Cnr2-/- mice were also evaluated. Het mice developed reverse tolerance (RT) to MAP-enhanced locomotor activity, and RT reduced the %PPI compared to wild-type (WT) mice. DAT-Cnr2-/- mice showed an increased sensitivity to stereotypical behavior induced by MAP and developed RT to MAP. DAT-Cnr2-/- mice exhibit a reduction in %PPI and alter social interaction, another core symptom of schizophrenia. These results demonstrate that there is an interaction between neuronal CB2R and MAP treatment, which increases the risk of schizophrenia-like behavior in this mouse model. This finding provides evidence for further studies targeting CB2R as a potential schizophrenia therapy.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Progress in neuro-psychopharmacology & biological psychiatry
- 巻
- 号
- 開始ページ
- 110924
- 終了ページ
- 110924
- 出版年月
- 2023年12月20日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.pnpbp.2023.110924
- 共同研究・競争的資金等の研究課題