Social behavioral changes in MPTP-treated monkey model of Parkinson's disease

Abstract

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 CLD-presymptomatic 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.

Behavioral phenotypes associated with MPTP induction of partial lesions in common marmosets ( Callithrix jacchus )

“…While males receiving a partial MPTP dose were somewhat impacted by motor deficit, males receiving the full MPTP dose were more prone to exhaustion-like behavior following the intrusion. These results are similar to those of Durand et al [33], who reported changes in social relationships in female rhesus monkeys ( Macaca mulatta ) treated with MPTP (with both low and high dose regimens). Such changes occurred before motor or cognitive impairments were detected and were most common in subordinate animals.…”

What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson’s disease?

“…For instance, MPTP lesions in monkey can lead to a decrease in behavioral activity 117 and goal-directed behaviors, 118 , 119 and to social behavioral changes. 120 However, because of the lack of neuroanatomical selectivity of systemic MPTP administration, and despite in-depth multi-correlational and neuroimaging analyses, it has yet to be determined from these studies whether these behavioral impairments result from a loss of dorso- or ventro-striatal function.…”

How Relevant Are Imaging Findings in Animal Models of Movement Disorders to Human Disease?

“…The faster peripheral metabolism in small rodents may render the use of some tracers problematic and has led to misrepresentation of their utility: an example of a tracer where this has been an issue is 18 F-DOPA which is under-used in rodents but extensively used in large animal models [13,16,17,21]. Recent studies using inhibitors to slow or reduce its peripheral metabolism have shown that both 18 F-DOPA uptake and dopamine turnover can be measured in rodents despite the faster tracer metabolism [74].…”