Abstract
Apathy is considered to be a core feature of Parkinson’s disease (PD) and has been associated with a variety of states and symptoms of the disease, such as increased severity of motor symptoms, impaired cognition, executive dysfunction and dementia. Apart from the high prevalence of apathy in PD, which is estimated to be about 40%, the underlying pathophysiology remains poorly understood and current treatment approaches are unspecific and proved to be only partially effective. In animal models, apathy has been sub-optimally modeled, mostly by means of pharmacological and stress-induced methods, whereby concomitant depressive-like symptoms could not be ruled out. In the context of PD only a few studies on toxin-based models (i.e., 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)) claimed to have determined apathetic symptoms in animals. The assessment of apathetic symptoms in more elaborated and multifaceted genetic animal models of PD could help to understand the pathophysiological development of apathy in PD and eventually advance specific treatments for afflicted patients. Here we report the presence of behavioral signs of apathy in 12 months old mice that express only ~5% of the vesicular monoamine transporter 2 (VMAT2). Apathetic-like behavior in VMAT2 deficient (LO) mice was evidenced by impaired burrowing and nest building skills, and a reduced preference for sweet solution in the saccharin preference test, while the performance in the forced swimming test was normal. Our preliminary results suggest that VMAT2 deficient mice show an apathetic-like phenotype that might be independent of depressive-like symptoms. Therefore VMAT2 LO mice could be a useful tool to study the pathophysiological substrates of apathy and to test novel treatment strategies for apathy in the context of PD.
Highlights
About 40% of all patients with Parkinson’s disease (PD) are estimated to suffer from apathy, a behavioral syndrome that is characterized by loss of or diminished motivation for goal-directed actions, affecting behavior, emotions and cognition (Robert et al, 2009; Pagonabarraga et al, 2015)
In this study we aimed at evaluating the usefulness of vesicular monoamine transporter 2 (VMAT2) deficient mice as a tool to study apathy-like symptoms in the context of PD
Animal models of PD presenting apathy-like symptoms in the absence of depressive-like symptoms are desirable for the study of apathy’s underlying processes and the development of specific treatments
Summary
About 40% of all patients with Parkinson’s disease (PD) are estimated to suffer from apathy (den Brok et al, 2015), a behavioral syndrome that is characterized by loss of or diminished motivation for goal-directed actions, affecting behavior, emotions and cognition (Robert et al, 2009; Pagonabarraga et al, 2015). The progression of apathy in PD is rather linked to the progression of the typical motor-symptoms than with depression (Zahodne et al, 2012), probably indicating independent roots for both conditions in the context of PD In this line, apathy might be associated with a hypodopaminergic state in the mesocorticolimbic pathway in PD (Czernecki et al, 2008; Pagonabarraga et al, 2015), lesions and neuroimaging studies suggest the dysfunction of frontal-subcortical circuits, especially those linking the ventromedial prefrontal cortex to related regions in the basal ganglia, to be relevant for the development of apathy (van Reekum et al, 2005; Levy and Czernecki, 2006; Chase, 2011; Santangelo et al, 2013; Robert et al, 2014). To differentiate apathetic-like from depressive-like symptoms we used the forced swimming test, a widely used test to assess signs of depression in rodents (Borsini and Meli, 1988; Bourin et al, 1998; Cryan et al, 2005; Petit-Demouliere et al, 2005)
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