Efeito da combinação de canabidiol e delta-9-tetraidrocanabinol em modelo de comportamento de doença induzido por lipopolissacarídeo em camundongos

Abstract

Cannabis sativa is a plant with ancient medicinal properties that has been used to treat symptoms of disorders that affect mechanisms related to the central nervous system (CNS). The sickness behavior is an inflammation-mediated process that affects cognitive processes. The present research investigated the attenuation effects on sickness behavior of cannabidiol (CBD) and its combination with Delta-9-tetrahydrocannabinol (THC), and the associated mechanisms in the animal model of sickness behavior induced by lipopolysaccharide (LPS). In the experiments, female C57BL/6 animals received LPS (0.5 mg/kg, i.p.) for 10 days. From the 6th to the 10th day, the animals were treated with CBD 20 mg/kg or CBD+THC (10:1) at the doses of 10 and 20 mg/kg. From the 8th to the 10th day, the animals were submitted to forced swimming (NF), tail suspension (SC), open field (CA) and social interaction (IS) tests. On the eleventh day, the animals were euthanized, and the prefrontal cortex (PFC) was dissected. The relative mRNA expression of genes related to the inflammatory response (IL-6, TNF-α, TLR4 and KMO), synaptic markers (PSD95 and NEDD8), brain-derived neurotrophic factor receptors (p75 and TRKB), glutamate receptor (NR2B), enzymes and receptors of the endocannabinoid system (MAGL, FAAH, CB1 and CB2) were evaluated. The CBD+THC 10 mg/kg treatment showed better effect in attenuating LPS-induced immobility in NF and SC. As for gene expression, there was attenuation of IL-6 expression in animals treated with cannabinoids, with CBD+THC 10 mg/kg showing a higher level of the interleukin downregulation, whereas treatment with CBD+THC 20 mg/kg had an increase in gene expression of the MGLL, FAAH and CB1 genes. In conclusion, the combination CBD+THC 10 mg/kg seemed to be the most suitable to attenuate the behavioral and inflammatory changes induced by LPS.