The role of HINT1 in methamphetamine-induced behavioral sensitization.

Abstract

Drug addiction is a chronically relapsing disorder in humans yet the underlying mechanism remained unclear. Recent studies suggested that histidine triad nucleotide binding protein1 (HINT1) may play significant roles in diverse neuropsychiatric diseases including drug addiction. In the current study, we used different batches of mice to establish different stages of methamphetamine (METH)-induced behavioral sensitization (BS) to explore the dynamic changes throughout the process of addiction in different brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), and hippocampus (Hip). In addition, we used HINT1 knockout (KO) mice to investigate the effect of HINT1 protein deletion on METH-induced BS. We found that in PFC of the METH group mice, the HINT1 expression level initially increased after development phase, and then dropped to the normal level during expression phase. However, there was no statistical difference in the HINT1 expression level in the other three encephalic regions (NAc, CPu, and Hip). The absence of HINT1 could promote METH-mediated addictive behavior to a certain extent, while the significant difference between genotypes only occurred in the development phase. Using the new technique, hip fractures were correctly predicted in 78% of cases compared with 36% when using the T-score. The accuracy of the prediction was not greatly reduced when using SSM and SAM (78% and 74% correct, respectively). Various geometric and BMD distribution traits were identified in the fractured and non-fractured groups.