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Accepted manuscript

Cannabidiol improves nonmotor symptoms, attenuates neuroinflammation and favors hippocampal newborn neuronal maturation in a rat model of Parkinsonism

Published online by Cambridge University Press:  21 May 2024

Bianca Andretto de Mattos Open the ORCID record for Bianca Andretto de Mattos [Opens in a new window] ,
Jéssica Mendes Bonato Open the ORCID record for Jéssica Mendes Bonato [Opens in a new window] ,
Maria Clara Splendor Open the ORCID record for Maria Clara Splendor [Opens in a new window] ,
Elaine Del Bel Open the ORCID record for Elaine Del Bel [Opens in a new window] ,
Humberto Milani Open the ORCID record for Humberto Milani [Opens in a new window]  and
Rúbia Maria Weffort de Oliveira Open the ORCID record for Rúbia Maria Weffort de Oliveira [Opens in a new window]
Bianca Andretto de Mattos
Affiliation:
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.
Jéssica Mendes Bonato
Affiliation:
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.
Maria Clara Splendor
Affiliation:
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.
Elaine Del Bel
Affiliation:
Department of Basic and Oral Biology, School of Medicine, USP, Av. Bandeirantes, 14015-000, Ribeirão Preto, São Paulo, Brazil
Humberto Milani
Affiliation:
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.
Rúbia Maria Weffort de Oliveira*
Affiliation:
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.
*
*Corresponding author: Rúbia Maria Weffort de Oliveira, Phone: +55 44 30115165, Fax: +55 44 30114999, E-mail: rmmwoliveira@uem.br, Postal address: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.
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Abstract

Objective:

To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions.

Methods:

Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioral paradigms to evaluate nonmotor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis.

Results:

6-hydroxydopamine-lesioned rats exhibited memory impairments and despair-like behavior in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. Cannabidiol decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behavior that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favored the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats.

Conclusion:

The present findings suggest a potential beneficial effect of CBD on nonmotor symptoms induced by intra-nigral 6-OHDA infusion in rats.

Keywords

6-OHDA lesioncannabidiolmemoryhippocampal neurogenesisneuroinflammation
Type
Original Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 30
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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