Correlation of dopaminergic and serotonergic dysfunction in a rat model of Parkinson's disease

Abstract

Depression frequently accompanies Parkinson’s disease (PD) and has a great impact on patients’ quality of life and disease progression. Previous research suggested that dopamine and serotonin systems are closely linked with depression in PD. However, comprehensive studies about the relationship between these two neurotransmitter systems are limited. Therefore, the purpose of this study is to evaluate the effect of dopaminergic destruction on the serotonergic system in the same subject by using consecutive PET imaging. The interconnection between motor symptoms and depression was also examined. [18F]FP-CIT was applied to assess dopamine transporters and serotonin 1A (5-HT1A) receptors were evaluated by [18F]Mefway in unilateral 6-hydroxydopamine (6-OHDA) lesioned and sham operated rats. Behavioral tests were used to evaluate the severity of symptoms: rotational number for motor impairment and immobility time, acquired from the forced swim test for depression. Region-of-interests (ROIs) were drawn in the striatum and cerebellum for the dopamine system and hippocampus and cerebellum for the 5-HT system. Non-displaceable binding potential in the striatum and hippocampus were compared between 6-OHDA and sham groups. As a result, unilateral 6-OHDA-lesioned rats exhibited significant bilateral reduction of hippocampal BPND for 5-HT1A receptors compared with the sham group and there was a positive correlation between striatal BPND for DAT. The severity of motor symptoms was also closely related to the depression. Taken together, the data demonstrate that destruction of the dopaminergic system causes the reduction of the serotonergic system and that the degrees of change in these neurotransmitter systems are also related with behavioral impairment in PD.