Lateral habenula as a link between dopaminergic and serotonergic systems contributes to depressive symptoms in Parkinson's disease

• We examined whether LHb lesions improve depressive symptoms of PD rats by increasing 5-HT levels of RN.
• LHb showed an obviously elevated cytochrome c oxidase in PD rats with depressive-like behavior.
• LHb lesions decreased the immobility time of FST in PD rats with depressive-like behavior.
• LHb lesions increased the climbing time of FST in PD rats with depressive-like behavior.
• LHb lesions increased the 5-HT levels of raphe nuclei in PD rats with depressive-like behavior.

Degeneration of substantia nigra dopaminergic neurons is a key pathological change of Parkinson's disease (PD), and its motor consequences have been widely recognized. Recently, mood disorders associated with PD have begun to attract a great deal of interest, however, their pathogenesis remains unclear. PD is associated with not only degenerative changes in dopaminergic neurons in the substantia nigra but also changes in serotonergic neurons in the raphe nuclei. The abnormalities in central 5-hydroxytryptamine (5-HT) neurotransmission are thought to play a key role in the pathogenesis of depression. The lateral habenula (LHb) is closely related to the substantia nigra and raphe nuclei, and its hyperactivity is closely related to the pathogenesis of depression. In this study, we screened rats with depressive-like behaviors from PD model animals and found that cytochrome c oxidase activity in the LHb of these rats was twice that seen in the control rats. In the forced swim test, LHb lesions caused a decrease in depressive-like behavior of PD rats as indexed by decreased immobility times and increased climbing times. Additionally, LHb lesions caused an enhance in 5-HT levels in the raphe nuclei. These results suggest that LHb lesions may improve depressive-like behavior in PD rats by increasing 5-HT levels in the raphe nuclei. Thus, LHb contributes to the depressive-like behavior in PD rats via mediating the effects of dopaminergic neurons in the substantia nigra on serotonergic neurons in the raphe nuclei.