Sandip Ghimire, Fabian Kreilaus, Rossana Rosa Porto, Lyndsey L Anderson, Justin J Yerbury, Jonathon C Arnold, Tim Karl
{"title":"Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1<sup>G93 A</sup>) mouse model of amyotrophic lateral sclerosis.","authors":"Sandip Ghimire, Fabian Kreilaus, Rossana Rosa Porto, Lyndsey L Anderson, Justin J Yerbury, Jonathon C Arnold, Tim Karl","doi":"10.1007/s00213-025-06785-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1<sup>G93A</sup>).</p><p><strong>Methods: </strong>Male and female SOD1<sup>G93A</sup> and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.</p><p><strong>Results: </strong>CBD treatment ameliorated the bodyweight loss in female SOD1<sup>G93A</sup> mice, tended to reinstate sociability in SOD1<sup>G93A</sup> males, strengthened social recognition memory in SOD1<sup>G93A</sup> females, and improved the PPI response in younger SOD1<sup>G93A</sup> females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1<sup>G93A</sup> mice and decreased the acoustic startle response and strengthened cue freezing in male mice.</p><p><strong>Conclusion: </strong>Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1<sup>G93A</sup> mice in a sex specific manner without altering the motor phenotype.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06785-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1G93A).
Methods: Male and female SOD1G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.
Results: CBD treatment ameliorated the bodyweight loss in female SOD1G93A mice, tended to reinstate sociability in SOD1G93A males, strengthened social recognition memory in SOD1G93A females, and improved the PPI response in younger SOD1G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.
Conclusion: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1G93A mice in a sex specific manner without altering the motor phenotype.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
