Vivian Hsu
China Medical University, Taiwan
Title: Blockage of system xc- improves cocaine addiction in cocaine-dependence mice
Biography
Biography: Vivian Hsu
Abstract
The cystine-glutamate antiporter or system xc- is a membrane-bound Na+-independent amino acid transporter which exchanges intracellular glutamate for extracellular cysteine. Previous studies have shown that activation of system xc- by its activator N-acetylcysteine (NAC) inhibits reinstated cocaine or nicotine seeking behaviors. In addition, the expression of system xc- subunit xCT in brain was up-regulated in cocaine dependence mice, but down-regulated in cocaine withdrawal mice, suggesting a dynamic change in xCT expression and its activity during addiction. Unfortunately, system xc- is not the only target for NAC and all pharmacological inhibitors commonly used to study system xc- activity have off-target effects. These issues raise the uncertain role of system xc- in addiction. In this study, we tested xCT knockout (xCT-/-) mice for dependence-induced drinking using the chronic intermittent cocaine-two bottle choice drinking protocol. There was significant inhibition in daily cocaine consumption in xCT-/- mice during free-choice drinking as compared to wild type (WT) mice, indicating genetic deficiency of system xc- blocked cocaine dependence. Moreover, sulfasalazine (SAS), the US Food and Drug Administration (FDA) that ã„“blocks system xc-, significantly attenuated the daily cocaine consumption during free-choice drinking in cocaine-dependence mice as compared to control vehicle (DMSO). Taken together, these findings show blockage of system xc- improves cocaine addiction in cocaine dependence-mice. Inhibition of system xc- represents a new class of therapeutics against cocaine addiction.