Serotonin and dopamine depletion in distinct brain regions may cause anxiety in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice as a model of early Parkinson's disease.

Abstract

In this study, we aimed to evaluate the association of early anxious behavior with serotonin, dopamine, and their metabolites in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease. Forty C57BL/6 male mice were randomly divided into the control group (n = 20) and the model group (n = 20). Mice in the model group were injected intraperitoneally with MPTP. The light-dark box (LDB) and elevated plus-maze were used to monitor anxious behavior. The association of early anxious behavior with neurotransmitters in the prefrontal cortex, hippocampus, and striatum was evaluated. In our murine model, MPTP induced a decreased level of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, hippocampus, and striatum (all P < 0.05); however, it only induced a decreased level of dopamine and its metabolite homovanillic acid (HVA) in the striatum (both P < 0.001), with a negative correlation in the hippocampus and a positive correlation in the cortex and striatum. In the LDB, 5-hydroxytryptamine levels in the cortex and dopamine and HVA levels in the striatum were negatively correlated with anxious behavior. Moreover, in the elevate plus-maze, 5-hydroxytryptamine and 5-HIAA in the cortex and dopamine and HVA in the striatum were positively correlated with the ratio of the time spent in open arms. In the murine model of early Parkinson's disease, the balance between dopamine and 5-hydroxytryptamine systems varied among brain regions. The depletion of 5-hydroxytryptamine in the cortex and dopamine in the striatum may be associated with anxiety behaviors in MPTP-treated mice.