Involvement of Raphe Nuclei in Depressive-like Behaviors and Short-Term Memory in an Animal Model of Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor symptoms and nonmotor disturbances such as fatigue, cognitive impairment, constipation, anxiety, and depression. The dopaminergic neurodegeneration is a hallmark of PD; however, the serotonergic system also presents alterations. Dorsal raphe nucleus (DRN) and median raphe nucleus (MNR) neurons are responsible for the central biosynthesis of serotonin (5-HT). We aimed to investigate whether the rotenone model would affect serotonergic neurons of the DRN and MRN and reduce 5-HT levels in target structures related to depressive-like behavior and short-term memory. Adult male Wistar rats were treated for 10 days with rotenone or sunflower oil. One day after the last rotenone injection, animals exhibited hypolocomotion in the open field. Furthermore, rotenone impaired the short-term memory assessed in the social recognition test performed 22 days after the last injection. In the forced swim test, performed on day 28, we observed depressive-like behavior, indicated by an increase in immobility time in the rotenone group. Immunohistochemical analysis revealed a reduction of serotonergic neurons in the MRN on the 28th day after the last administration of rotenone. Moreover, the ventrolateral part of DRN presented a decrease of serotonergic neurons. Neurochemical quantification revealed a reduction of serotonin levels in the prefrontal cortex and striatum, and a reduction of dopamine and noradrenaline levels in the prefrontal cortex, striatum, and amygdala. Overall, the results revealed that the development of behavioral impairments induced by systemic rotenone is involved with MRN, and likewise 5-HT, other neurotransmitters such as dopamine and noradrenaline may play a role in nonmotor disorders in the animal model of PD.