Sébastien CARNICELLA

DOPAMINERGIC NIGROSTRIATAL SYSTEM AND MOTIVATIONAL DEFICITS IN PARKINSON'S DISEASE: INSIGHTS INTO THE DARK SIDE OF THE MOON

Sébastien CARNICELLA
Institut des Neurosciences, Grenoble

Summary:Parkinson’s disease (PD) is a progressive neurodegenerative disorder occurring as a result of the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Beyond the characteristic motor features of the disease, PD is associated with a plethora of neuropsychiatric and cognitive impairments that range from dramatic deficits in hedonic processes, including decrease in motivated behaviors (apathy), anxiety and depression, to psychosis and compulsive behaviors.

Through the development of an experimental, lesion-based, model in rats, we recently showed that motivational and affective deficits in PD may directly stem from the loss of DA neurons within the SNc, thereby appearing as a core impairment of the disease. Moreover, our work also point toward a crucial role of D3 receptors in mediating the therapeutical effect of DA pharmacological treatments on such neuropsychiatric symptoms. This new insight into the pathophysiological mechanisms of mood and motivational dysfunctions in PD may therefore facilitate the design of new treatments.