Preventive Beneficial Effects of Cannabidiol in a Reserpine-Induced Progressive Model of Parkinsonism

Alvaro Costa Lima ¹ Vinicius dos Santos Bioni ¹ Marcela Becegato ¹ Ywlliane S. R. Meurer ¹ Debora Maria Cunha ¹ Nathan A Aguiar ¹ Fernanda Fiel Peres ¹ Antonio Waldo Zuardi ² Jaime Eduardo Hallak ² Soraya S Smaili ¹ Vanessa C Abílio ¹ Regina H Silva ^1*

• ¹ Federal University of São Paulo, São Paulo, Brazil
• ² Universidade de São Paulo, Ribeirão Preto, Brazil

Parkinson's disease (PD) is characterized by motor and non-motor symptoms such as tremors, difficulty in initiating movements, depression, and cognitive deficits. The pathophysiology of PD involves a gradual decrease in dopaminergic neurons in the substantia nigra, increased inflammatory parameters, and augmented oxidative stress in this region. Several new therapies aim to promote antioxidant and anti-inflammatory actions, including the use of cannabinoids, particularly cannabidiol (CBD). CBD is a non-psychotomimetic component of Cannabis sativa that acts broadly through several mechanisms. The objective of this study was to investigate the potential protective effect of CBD in mice subjected to a low-dose (0.1 mg/kg) repeated reserpine protocol, which encompasses behavioral and neuronal alterations compatible with the progressiveness of PD alterations. We used two approaches: (1) concurrent administration during the development of parkinsonism and (2) preadministration to explore possible preventive action. The effect of CBD (0.5 mg/kg) on reserpineinduced alterations was investigated on behavioral (catalepsy and vacuous chewing movements) and neuronal (immunolabeling for tyrosine hydroxylase -TH) parameters. Overall, groups that were treated with CBD and reserpine presented motor alterations later during the protocol compared to the groups that received only reserpine (except for vacuous chewing evaluation in the concomitant treatment). Additionally, CBD attenuated reserpine-induced catalepsy (preventive treatment) and prevented the decrease in TH labeling in the substantia nigra pars compacta in both concurrent and preventive protocols. Based on these data, we observed a beneficial effect of CBD in motor and neuronal alterations reserpine-induced progressive parkinsonism, particularly after preventive treatment.