Relationship between dopamine deficit and the expression of depressive behavior resulted from alteration of serotonin system

Abstract

Depression frequently accompanies in Parkinson's disease (PD). Previous research suggested that dopamine (DA) 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 serotonin system. The interconnection between motor and depression was also examined. Two PET scans were performed in the 6-hydroxydopamine (6-OHDA) lesioned and sham operated rats: [(18) F]FP-CIT for DA transporters and [(18) F]Mefway for serotonin 1A (5-HT(1A)) receptors. Here, 6-OHDA is a neurotoxin for dopaminergic neurons. 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 were drawn in the striatum and cerebellum for the DA system and hippocampus and cerebellum for the 5-HT system. The cerebellum was chosen as a reference region. Nondisplaceable binding potential in the striatum and hippocampus were compared between 6-OHDA and sham groups. As a result, the degree of DA depletion was negatively correlated with rotational behavior (R(2) = 0.79, P = 0.003). In 6-OHDA lesioned rats, binding values for 5-HT(1A) receptors was 22% lower than the sham operated group. This decrement of 5-HT(1A) receptor binding was also correlated with the severity of depression (R(2) = 0.81, P = 0.006). Taken together, this research demonstrated that the destruction of dopaminergic system causes the reduction of the serotonergic system resulting in the expression of depressive behavior. The degree of dopaminergic dysfunction was positively correlated with the impairment of the serotonin system. Severity of motor symptoms was also closely related to depressive behavior.