Early-onset Parkinsonian behaviors in female Pink1-/- rats.

Parkinson disease (PD) is a progressive, neurological disease that affects millions of individuals worldwide. Although instability, rigidity, tremor, and bradykinesia are considered hallmark motor signs of the disease, these are not apparent until mid-to-late stage. In addition to limb motor impairment, individuals with PD also exhibit early-onset speech dysfunction and reduced vocal intelligibility as well as anhedonia and anxiety. Many of these clinical signs vary according to sex in humans with PD. In this study, a translational genetic rat model of early-onset PD (Pink1-/-) was used to address significant gaps in knowledge concerning sex-specific characteristics of limb sensorimotor deficits, vocal motor dysfunction, and changes in affective state. Traditional behavioral tests of limb function, ultrasonic vocalization, anxiety, and anhedonia in the Pink1-/- female rat and wildtype controls were used to test the hypothesis that behavioral performance would significantly differ between genotypes, and that these differences would increase with disease progression (age of the rat). Results demonstrate that Pink1-/- female rats do not exhibit limb sensorimotor deficits but do have significantly reduced intensity (loudness) of vocalizations, and present with anhedonia and anxiety by 8 months of age. Consistent with an early-disease model, Pink1-/- female rats do not exhibit significant decreases in nigrostriatal catecholamines/metabolites, as measured by HPLC. These results are significant in expanding knowledge of early-onset deficits in the female Pink1-/- genetic rat model of PD.