Candidate genes or compounds for therapeutic tools against methamphetamine and/or morphine-induced dependence

Drug dependence is one of most severe problems in all over the world, however, the mechanisms and related-genes have not been completely revealed. Here we would like to introduce tumor necrosis factor-α (TNF-α). Repeated treatment with methamphetamine induced an increase in TNF-α mRNA in the some brain regions. Exogenous TNF-α blocked the methamphetamine rewarding. TNF-α plays a neuroprotective role in methamphetamine drug dependence. These results suggest that TNF-α is one of key proteins. TNF-α itself might not be therapeutic tools, since it has immunological actions in physical conditions. Therefore, next, we found a stimulator, Leu-Ile, which enhances TNF-α synthesis in cultured neurons. Leu-Ile protected blocked the methamphetamine-induced rewarding effects. These results suggest that a stimulator of TNF-α synthesis may be one of therapeutic tools against drug dependence.