The dorsal raphe nucleus (DRN) contains the largest group of serotonin-producing neurons, and changes in DRN function have been implicated in neuropsychiatric diseases and movement disorders ( Hornung, 2010 Huot et al., 2011). However, long-term use of L-DOPA leads to the development of dyskinesias and non-motor manifestations ( Espay et al., 2018), showing that the pathological process extends beyond the dopaminergic system and that other neurotransmitter systems such as the serotonergic system are involved. Dopamine replacement therapy using the precursor L-DOPA is the main treatment for the disease. Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, which is characterized by the progressive loss of dopaminergic neurons in the substantia nigra compacta (SNc). We also discuss the role of the serotonergic system in LID and if therapeutic approaches specifically targeting this system may constitute an effective strategy in PD. In this review article, we summarize the interactions between the serotonergic and other systems. Consistent with this, the administration of serotonergic agonists suppressed LID. This mechanism may also be involved in the development of graft-induced dyskinesias (GID), possibly due to the inclusion of serotonin neurons in the grafted tissue. The lack of any autoregulatory feedback control in serotonergic neurons to regulate L-DOPA-derived dopamine release contributes to the appearance of L-DOPA-induced dyskinesia (LID). Serotonergic terminals can convert L-DOPA to dopamine, which mediates dopamine release as a “false” transmitter. Interestingly, serotonergic neurons play an important role in the effects of L-DOPA in advanced PD stages. Moreover, serotonergic dysfunction also causes motor symptoms. Interaction between the serotonergic and other neurotransmitters systems such as dopamine, noradrenaline, glutamate, and GABA controls the activity of striatal neurons and are particularly interesting for understanding the pathophysiology of PD. This pathology reduces patient quality of life. Serotonergic dysfunction is associated with non-motor symptoms and complications, including anxiety, depression, dementia, and sleep disturbances. However, other non-dopaminergic neuronal systems such as the serotonergic system are also involved. Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. 3Department of Clinical Neurology, Hospital Alvaro Cunqueiro, University Hospital Complex, Vigo, Spain.2Networking Research Center on Neurodegenerative Diseases (CiberNed), Madrid, Spain.1Laboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Deptartment of Morphological Sciences, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.Ana Muñoz 1,2*, Andrea Lopez-Lopez 1,2, Carmen M.
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