ReferenceID 4830

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

Front Cell Neurosci

Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it's potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescenc

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Reference Id
4830
Evidence Id
21420
Core Evidence Id
21420
Source Reference Id
2910
Herb2 Reference Id
HBREF003707
Subject Paper Key
HBIN019558_36406747
Pubmed Id
36406747
Doi
10.3389/fncel.2022.1010478
Paper Title
The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia
Paper Abstract
Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it's potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous ( Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ 9 -tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains.
Journal
Front Cell Neurosci
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Cannabidiol; Chronic Adolescent; Schizophrenia; Adolescent Cbd
Paper Title Cn
Paper Title En
The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia
Bilingual Status
semi_complete