L-DOPA-induced dysregulation of extrastriatal dopamine and serotonin and affective symptoms in a bilateral rat model of Parkinson's disease

► A novel bilateral rat model of Parkinson's disease resulted in loss of approximately 80% striatal DA. ► Chronic L-DOPA-induced time-dependent imbalances in DA/5-HT levels in extrastriatal brain areas. ► Prior exposure to L-DOPA did not damage DA and 5-HT neurons. ► Anxiogenic effects of chronic L-DOPA were observed in bilateral-lesioned rats during the OFF phase.