Preliminary Evidence of Apathetic-Like Behavior in Aged Vesicular Monoamine Transporter 2 Deficient Mice

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.

Neuropsychiatric Disorders in Parkinson’s Disease: What Do We Know About the Role of Dopaminergic and Non-dopaminergic Systems?

“…Lesion of the medial part of VTA did not induce such a behavior, indicating that damage of the nigrostriatal pathway is a key risk factor to develop apathy-like behavior in the 6-OHDA rat model of PD. Another study did report behavioral signs of apathy in aged mice deficient for the vesicular monoamine transporter 2 (Baumann et al, 2016).…”

Positive modulation of cerebellar α6GABAAreceptors for treating essential tremor: a proof-of-concept study in harmaline-treated mice

“…The burrowing activity in laboratory rodents is one of their "Activities of Daily Living" (ADL) (Deacon, 2012), and has been used as an indicator of well-being (Jirkof, 2014), because it is negatively associated with stress (Van Loo et al, 2007) or chronic pain (Huang et al, 2013) in rodents. In addition, a deficit of the burrowing activity has also been reported in mouse models of neurodegenerative diseases, such as Alzheimer's disease (Geiszler et al, 2016) and Parkinson's disease (Baumann et al, 2016). The finding that harmaline markedly disrupted the burrowing activity in mice (Fig.…”

Neuropsychiatric and Cognitive Deficits in Parkinson’s Disease and Their Modeling in Rodents

“…Since several years, apathy has been defined as a distinct NMS of PD, that can occur independently of depression [ 26 ]. Apathy disorder can be estimated with the MMSE and the Dimensional Apathy Scale (DAS).…”