Approximately 45% of patients suffering from Parkinson's disease (PD) are affected by depressive disorders. However, the pathophysiology of PD-associated depression remains largely unknown. In the present study, we determined the monoamine content of the hippocampus (HIP) and the prefrontal cortex (PFC), structures related to depression, and of the striatum in the bilateral 6-hydroxydopamine (6-OHDA) rat model. Rats were lesioned bilaterally in the substantia nigra pars compacta or the striatum. One or two weeks after the lesion, the levels of dopamine (DA), noradrenaline (NAD) and serotonine (5-HT) were determined by LC in homogenates of the various brain regions. Striatal DA levels decreased in striatally and nigrally lesioned rats by respectively 50% and 90% compared to control rats. The DA levels in the HIP and PFC showed a trend to reduce in both protocols one week after the lesion and restored to baseline levels two weeks post-lesioning. There was no significant effect of the two lesion protocols on 5-HT levels in all regions studied, only a brief decrease in the HIP 1 week after the nigral lesion was observed. Finally, these lesions resulted in significantly decreased hippocampal and PFC NAD levels up to approximately 50% compared to controls. Nigrostriatal degeneration alters the NAD content of the HIP and PFC but has no important effect on 5-HT levels. No clear effects on DA levels were observed in the HIP and PFC in both lesion protocols. Striatal and nigral lesions resulted in similar effects on monoamine content in depression-related brain structures. These findings could contribute to a better understanding of depression in PD.