Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain

• Published in: Pharmacological reports 2021-12, Vol.73 (6), p.1680-1693
• Main Authors: Tito, Pedro Augusto Lopes, Bernardino, Túlio Cézar de Souza, Bellozi, Paula Maria Quaglio, da Silva, Maria Carolina Machado, de Miranda, Aline Silva, Vieira, Érica Leandro Marciano, Moreira, Fabrício A., Palotás, András, de Oliveira, Antônio Carlos Pinheiro, Reis, Helton José
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Brain - drug effects; Brain - metabolism; Brain-Derived Neurotrophic Factor - metabolism; Cannabidiol - pharmacology; Cytokines - metabolism; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - physiopathology; Disease Models, Animal; Drug Safety and Pharmacovigilance; Illness Behavior - drug effects; Lipopolysaccharides; Male; Medicine; Mice; Mice, Inbred C57BL; Nerve Growth Factor - metabolism; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - physiopathology; Pharmacotherapy; Pharmacy
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1007/s43440-021-00301-8

Background Major depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects. Cannabidiol (CBD), a phytocannabinoid, exerts antidepressant-like effects in experimental animals. This study investigated the impact of CBD on sickness behavior (SB), a measure of depressive-like response, and neuro-immune changes induced by lipopolysaccharides (LPS) in mice. Methods Socially isolated rodents were administered with LPS to trigger SB. and treated with CBD or its vehicle. Animals were submitted to forced swimming test, to evaluate depressive-like behavior, and to open field test, to evaluate locomotory activity. Immediately after behavioral analyses, animals were euthanized and had their hypothalamus, prefrontal cortex and hippocampus dissected, to proceed neurotrophins and cytokines analyses. ELISA was used to detect IL-1β, BDNF and NGF; and cytometric beads array to measure IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10 levels. Results CBD effectively prevented SB-induced changes in the forced swim test without altering spontaneous locomotion. This phytocannabinoid also partially reversed LPS-evoked IL-6 increase in both the hypothalamus and hippocampus. In addition, CBD prevented endotoxin-induced increase in BDNF and NGF levels in the hippocampus of SB animals. Conclusions Apparently, CBD prevents both behavioral and neuro-immunological changes associated with LPS-induced SB, which reinforces its potential use as an antidepressant which modulates neuroinflammation. This opens up potentially new therapeutic avenues in MDD.