Proteomic and Behavioral Analysis of Response to Isoliquiritigenin in Brains of Acute Cocaine Treated Rats

Abstract

Isoliquiritigenin (ISL) is a licorice flavonoid with chalcone structure and is an active component of the root of the plant genus Glycyrrhiza. In addition to anti-inflammatory and antioxidant effects, ISL was previously reported to antagonize increased striatal dopamine release. In the present study, we aimed to investigate whether ISL has an effect on hyperlocomotion in animals subjected to acute cocaine administration and whether ISL modulates acute cocaine-induced molecular changes. To achieve our goals, we analyzed behavior and differential proteomic changes between ISL and vehicle in acute cocaine treated rats. Locomoter activity was reduced in ISL treated animals compared to vehicle in acute cocaine treated rats. Two dimensional electrophoresis (2-DE) revealed that 56 proteins were differentially expressed in response to ISL. Further proteomic analyses using mass spectroscopy, and subsequent validation experiments confirmed that ISL induced changes in proteins related to metabolism, signal transduction, protein folding and transport, oxidative stress, and neural toxicity. Furthermore, cocaine-induced neuronal toxicity was attenuated by ISL treatment, suggesting a neuroprotective role of ISL.