Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice

Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like...

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Main Authors: Madilyn Coles, Georgia Watt, Fabian Kreilaus, Tim Karl
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/full
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author Madilyn Coles
Georgia Watt
Fabian Kreilaus
Tim Karl
Tim Karl
author_facet Madilyn Coles
Georgia Watt
Fabian Kreilaus
Tim Karl
Tim Karl
author_sort Madilyn Coles
collection DOAJ
description Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and APPSwe/PS1ΔE9 (APPxPS1) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating. APPxPS1 mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in APPxPS1 mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but APPxPS1 mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated APPxPS1 mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of APPxPS1 mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice.
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spelling doaj.art-d14f1a9a4b7b452494409255110fff332022-12-21T23:19:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-12-011110.3389/fphar.2020.587604587604Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female MiceMadilyn Coles0Georgia Watt1Fabian Kreilaus2Tim Karl3Tim Karl4School of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaNeuroscience Research Australia, Randwick, NSW, AustraliaAlzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and APPSwe/PS1ΔE9 (APPxPS1) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating. APPxPS1 mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in APPxPS1 mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but APPxPS1 mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated APPxPS1 mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of APPxPS1 mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice.https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/fullAlzheimer’s diseaseAPPSwe/PS1ΔE9transgenic mouse modelcannabidioltreatmentbehavior
spellingShingle Madilyn Coles
Georgia Watt
Fabian Kreilaus
Tim Karl
Tim Karl
Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
Frontiers in Pharmacology
Alzheimer’s disease
APPSwe/PS1ΔE9
transgenic mouse model
cannabidiol
treatment
behavior
title Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
title_full Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
title_fullStr Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
title_full_unstemmed Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
title_short Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
title_sort medium dose chronic cannabidiol treatment reverses object recognition memory deficits of appswe ps1δe9 transgenic female mice
topic Alzheimer’s disease
APPSwe/PS1ΔE9
transgenic mouse model
cannabidiol
treatment
behavior
url https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/full
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