Kynurenine amplifies tetrahydrocannabinol-induced sensorimotor impairment and classic “tetrad” effects in mice

BackgroundL-kynurenine (KYN), a kynurenine pathway (KP) metabolite, is the main precursor for the neuroactive metabolite kynurenic acid (KYNA). Several studies suggest a patho-physiologically relevant association between increased brain KYNA levels and cognitive dysfunctions in individuals with schizophrenia. Δ9-tetrahydrocannabinol (Δ9-THC; i.e. the main psychoactive compound of cannabis) can worse schizophrenia-related psychosis, often leads to the development of cannabis use disorder in individuals with schizophrenia, and increases the risk of earlier onset of schizophrenia symptoms in those with a genetic predisposition. A role of KP alterations and, specifically, increased brain KYNA levels in Δ9-THC-induced psychotic symptoms has been previously proposed. The aim of the study was to investigate on the possible involvement of KP alterations in Δ9-THC-induced sensorimotor and “tetrad” responses in mice.