Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Strain, Sex, and Time Dependent Antidepressant-like Effects of Cannabidiol

Gabriela Pandini Silote
ORCID logo ,
Michelle C. Gatto
,
Amanda Eskelund
,
Francisco S. Guimarães
,
Gregers Wegener
ORCID logo ,
Sâmia R. L. Joca
*
Version 1 : Received: 19 October 2021 / Approved: 25 October 2021 / Online: 25 October 2021 (12:32:45 CEST)

A peer-reviewed article of this Preprint also exists.

Silote, G.P.; Gatto, M.C.; Eskelund, A.; Guimarães, F.S.; Wegener, G.; Joca, S.R.L. Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol. Pharmaceuticals 2021, 14, 1269. Silote, G.P.; Gatto, M.C.; Eskelund, A.; Guimarães, F.S.; Wegener, G.; Joca, S.R.L. Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol. Pharmaceuticals 2021, 14, 1269.

Abstract

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

Keywords

Cannabidiol; S-Ketamine; Sex; Mice strain; Flinders Sensitive Line rats; Tail suspension test; Forced Swim Test.

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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