Chronic cannabidiol (CBD) treatment did not exhibit beneficial effects in 4-month-old male TAU58/2 transgenic mice

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, motor impairments, and accumulation of hallmark proteins, amyloid-beta (Aβ) and tau. Traditionally, transgenic mouse models for AD have focused on Aβ pathology, however, recently a number of tauopathy transgenic models have been developed, including the TAU58/2 transgenic model. Cannabidiol (CBD), a non-toxic constituent of the Cannabis sativa plant, has been shown to prevent and reverse cognitive deficits in Aβ transgenic mouse models of AD. Importantly, the therapeutic properties of CBD on the behavioural phenotype of tauopathy mouse models have not been investigated.We assessed the impact of chronic CBD treatment (i.e. 50 mg/kg CBD i.p. administration starting 3 weeks prior to behavioural assessments) on disease-relevant behaviours of 4-month-old TAU58/2 transgenic males in paradigms for anxiety, motor functions, and cognition.TAU58/2 transgenic males demonstrated reduced body weight, anxiety and impaired motor functions. Furthermore, they demonstrated increased freezing in fear conditioning compared to wild type-like animals. Interestingly, both sociability and social recognition memory were intact in AD transgenic mice. Chronic CBD treatment did not affect behavioural changes in transgenic males.In summary, 4-month-old TAU58/2 transgenic males exhibited no deficits in social recognition memory, suggesting that motor deficits and changes in anxiety at this age do not impact on social domains. The moderate increase in fear-associated memory needs further investigation but could be related to differences in fear extinction. Future investigations will need to clarify CBD's therapeutic potential for reversing motor deficits in TAU58/2 transgenic mice by considering alternative CBD treatment designs including changed CBD dosing.