論文

査読有り 国際誌
2023年12月20日

Cannabinoid CB2 receptors and hypersensitivity to methamphetamine: Vulnerability to schizophrenia.

Progress in neuro-psychopharmacology & biological psychiatry
  • Ana Canseco-Alba
  • ,
  • Koichi Tabata
  • ,
  • Momoki Yukihiko
  • ,
  • Taharima Tabassum
  • ,
  • Yasue Horiuchi
  • ,
  • Tadao Arinami
  • ,
  • Emmanuel S Onaivi
  • ,
  • Hiroki Ishiguro

開始ページ
110924
終了ページ
110924
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.pnpbp.2023.110924

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.

リンク情報
DOI
https://doi.org/10.1016/j.pnpbp.2023.110924
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/38135096
ID情報
  • DOI : 10.1016/j.pnpbp.2023.110924
  • PubMed ID : 38135096

エクスポート
BibTeX RIS