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

Elodie Durand,Marlène Laurent,Odile Petit,Cédric Zimmer,Léon Tremblay,Bruno Pereira,Céline Silberberg,Franck Durif,Carine Chassain,Véronique Sgambato-Faure

doi:10.3389/fnbeh.2015.00042

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.

Highlights

Idiopathic Parkinson’s disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in decreased levels about 60% of dopamine release in the striatum and causing motor symptoms (Kish et al, 1988)
In addition to the lesion of the dopaminergic nigrostriatal system, other dopaminergic systems are damaged in PD, namely those originating in the ventral tegmental area (VTA) that project to the limbic system, which is involved in the reward circuit, and to the prefrontal cortex, which is involved in personality traits (Tzschentke, 2001; Haber and Knutson, 2010)
The first period corresponded to the Chronic High-Dose (CHD)-presymptomatic motor state, and included a significant increase in the clinical score compared to the CLDpresymptomatic motor state (3.1 ± 0.9 vs. 0.9 ± 0.6; t = 11.28, p < 0.001), the score stayed below the threshold value of 6

Summary

Introduction

Idiopathic Parkinson’s disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in decreased levels about 60% of dopamine release in the striatum and causing motor symptoms (bradykinesia, tremor and rigidity) (Kish et al, 1988). Psychiatric disorders include apathetic state (Pedersen et al, 2009; Thobois et al, 2010), anxiety (Gallagher and Schrag, 2012) and depression (Martínez-Martín and Damián, 2010) as well as hypomania, psychosis and impulse control disorders observed in patients receiving dopaminergic treatment (Weintraub et al, 2006; Ulla et al, 2012) The pathophysiology of such disorders has not yet been completely understood but includes lesions of the dopaminergic, serotoninergic, and noradrenergic systems involved in Parkinson’s disease (Hirsch et al., 2003; Kish et al, 2008). In addition to the lesion of the dopaminergic nigrostriatal system, other dopaminergic systems are damaged in PD, namely those originating in the ventral tegmental area (VTA) that project to the limbic system, which is involved in the reward circuit (mesolimbic system), and to the prefrontal cortex, which is involved in personality traits (mesocortical system) (Tzschentke, 2001; Haber and Knutson, 2010)

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