Abuse of volatile organic solvents among youth remains a major social problem in Japan. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a so-called "gate-way drug" for users. Psychological dependence assessment systems have been established for drug inhalation using the conditioned place preference (CPP) procedure. We found toluene produced the rewarding effect in this new CPP system. The mesolimbic dopamine pathway, which includes dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain and their targets in the limbic forebrain, especially the nucleus accumbens (NAC), is one of the most important substrates for the development of psychological dependence on drugs such as stimulants, cocaine, and heroin. Recently, it has indicated that the VTA-NAC pathway (monoamine system) may play an important role of the expression of psychological dependence on the volatile organic solvent toluene. Clarification of organic solvent's mechanism for the development of psychological dependence focusing on the monoamine system can be exploited for the new medicine and useful treatments for dependence on toluene.