Effects of a synthetic cannabinoid, 5F-MDMB-PICA, on metabolites and glutamatergic transporters in U87 cell line

Abstract

Brian metabolic pathways have been impaired in animals exposed to drugs of abuse. The misuse of cannabinoids is associated with neuronal death and synaptic plasticity. Astrocytic glutamate transporters are therapeutic targets in several preclinical models of substance use disorders. Abused drugs could impair metabolic pathways in animal models, particularly those involving astrocytes, where glutamate transporters are critical regulators of neurotransmission. We here aimed to evaluate the metabolomic profile of a human glioblastoma cell line following exposure a synthetic cannabinoid, 5F-MDMB-PICA (5F-M-P), using an in vitro cell model (U87, glioblastoma astrocytic origin cell line). Additionally, we evaluated the effects of 5F-M-P on the expression of astrocytic glutamate transporters. After treatments, the cells were collected for metabolomic study using gas chromatography-mass spectrometry, and protein expression study using western blotting assay. 5F-M-P, especially at a concentration of 100 μM, altered the abundance of numerous metabolites. Enrichment analysis identified that specific signaling pathways were involved in the effects of 5F-M-P on metabolites, including the glutamate neurotransmission pathway. Additionally, 5F-M-P at 200 μM reduced the expression of glutamate transporter-1 and glutamate-aspartate co-transporter. Therefore, 5F-M-P exposure altered key metabolic pathways in astrocytes including glutamatergic pathways, an effect associated with reduced astrocytic glutamate transporter expression.