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

Autor: Canseco-Alba A; Laboratory of Reticular Formation Physiology, National Institute of Neurology and Neurosurgery, Mexico City 14269, Mexico; Department of Biology, William Paterson University, Wayne, NJ 07470, USA., Tabata K; Department of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan., Momoki Y; Department of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan., Tabassum T; Department of Clinical Genetics, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan., Horiuchi Y; Department of Clinical Genetics, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan; Department of Genomic Medicine, Shizuoka Graduate University of Public Health, Shizuoka, Shizuoka 420-0881, Japan., Arinami T; Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan., Onaivi ES; Department of Biology, William Paterson University, Wayne, NJ 07470, USA., Ishiguro H; Department of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan; Department of Clinical Genetics, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3821, Japan. Electronic address: hishiguro@yamanashi.ac.jp.
Jazyk: angličtina
Zdroj: Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2024 Mar 02; Vol. 130, pp. 110924. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1016/j.pnpbp.2023.110924
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest None. There was no human subjects analyzed in this research. All animal procedures were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee of the University of Yamanashi (approval no: A29–45) and the William Paterson University Animal Care and Use Committee.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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