Social behavioral changes in MPTP-treated monkey model of Parkinson's disease
Résumé
Parkinsonian patients experience not only the physical discomfort of motor disorders
but also the considerable psychological distress caused by cognitive deficits and behavioral
disorders. These two factors can result in a disruption of social relationships during the
symptomatic and even the presymptomatic motor states of the disease. However, it remains
difficult, if not impossible, to evaluate social relationships in presymptomatic patients.
The present study focused on the evaluation of social relationships within a group of
female long-tailed macaques during presymptomatic and symptomatic motor states induced
by Chronic Low-Dose (CLD) and then Chronic High-Dose (CHD) systemic administration of
1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). Dopaminergic denervation within
basal ganglia and cortical areas was evaluated using Positron Emission Tomography (PET)
scans with 18F-DOPA (6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine) radiotracer.
Interestingly, social behavioral changes could be identified in the presymptomatic
motor state before any motor and/or cognitive impairment occurred. Stronger effects were
observed in subordinate animals compared to dominant animals. From baseline state to CLDpresymptomatic
motor state, the frequency of emitted affiliative and aggressive behaviors
increased. From CLD-presymptomatic to CHD-presymptomatic motor states, the frequency of
the three categories of social behaviors (aggressive, submissive and affiliative) decreased. At
this time, quantitative data analysis in PET scans highlighted a dopaminergic denervation in
the insula and the posterior caudate nucleus. Finally, the frequency of the three categories of
social behaviors decreased during the stable-symptomatic motor state compared to baseline
and presymptomatic motor states; this was also associated with motor and cognitive disorders
and a dopaminergic denervation in all the evaluated cortical and subcortical structures.