Prodromal timeline of a Parkinson’s disease model: anxiety-like behavior precedes cognitive and motor impairment.

CHAMPARINI L; HERRERA M.; COMETTO M; NARANJO A; CRESPO R; CALFA G; HEREÑU C

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Parkinson’s disease results from a progressive dopaminergic neuronal loss, characterized by multiple motor and non-motor symptoms. Currently, its diagnosis is based on motor deficits, but there is also a variety of previous and coexisting non-motor symptoms that result from dysfunction of interconnected systems. We aimed to determine, in a rat model of neurotoxicity, the progression of deficits on cognitive tasks and anxiety-like behavior before the onset of motor impairment. Animals, at day 0, were injected with 6-OHDA or with vehicle solution into the dorsolateral striatum (experimental or control groups, respectively). Independent groups of rats were tested only once in a behavioral task after 1, 2 and 3 weeks post lesion (Contextual fear conditioning, Y-maze, elevated plus maze, lightdark box test and locomotor activity test). We observed anxiety-like behavior 2 and 3 weeks post lesion. We observed working memory impairment in 6-OHDA rats after 3 weeks of neurodegeneration, without motor alterations. These results could be associated with a partial lesion of the nigrostriatal DA system as we found a decrease in tyrosine hydroxylase immunoreactivity in substantia nigra, ventral tegmental area, and striatum. We concluded that a single bilateral infusion of 6OHDA induced anxiety-like behavior before cognitive alterations that preceded locomotor deficits in the employed dopamine-depleted animal model.