A transgenic mouse disrupted a circadian clock-related gene showed increased locomotor sensitization and conditioned place preference toward methamphetamine

抄録

Drug addiction is a chronic brain disorder characterized by compulsive or uncontrolled drug use, despite adverse consequences. The process of drug addiction is thought to be affected by complex interplay of endogenous and exogenous factors. Additionally, increasing studies have reported that drug effect is correlated with circadian rhythm, in which the circadian-related genes, have been focused as the genes influencing drug addiction. Thus, this study investigated the role of one of the circadian-related genes in methamphetamine (METH)-induced dependence using the candidate gene-disrupted mutant (TG) mice. Before conducting METH-induced locomotor sensitization and reward experiments, the behavioral characteristics of TG mice were assessed. Withdrawal responses to METH were also observed on the 1st withdrawal day after 7 days METH treatments. After METH-induced locomotor sensitization, the expression levels of dopamine-related genes were measured in the striatum of the animals using qRT-PCR. We have found that TG mice showed higher locomotor sensitization response to chronic METH treatment and METH challenge. They also exhibited higher rewarding effects to METH than the Wildtype (WT) mice. In addition, the TG mice showed higher withdrawal responses and the total globe withdrawal score against METH than the WT mice. The expression levels of dopamine-related genes after chronic METH treatments suggested that these TG mice might have higher dopamine level than the WT. Taken together, the process of METH-induced dependence might be influenced by the expression level of the candidate gene probably with an interplay with the dopaminergic system. Further studies will be conducted to prove this hypothesis with the candidate gene overexpressing TG mice and other addictive drugs.