[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-alpha (TNF-alpha). Repeated treatment with methamphetamine induced an increase in TNF-alpha mRNA in the some brain regions. Exogenous TNF-alpha blocked the methamphetamine rewarding. TNF-alpha plays a neuroprotective role in methamphetamine drug dependence. These results suggest that TNF-alpha is one of key proteins. TNF-alpha 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-alpha synthesis in cultured neurons. Leu-Ile protected blocked the methamphetamine induced rewarding effects. These results suggest that a stimulator of TNF-alpha synthesis may be one of therapeutic tools against drug dependence.