title: What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson's disease?
abstract: In addition to classical motor symptoms, Parkinson's disease (PD) patients display incapacitating neuropsychiatric manifestations, such as apathy, anhedonia, depression and anxiety. These hitherto generally neglected non-motor symptoms, have gained increasing interest in medical and scientific communities over the last decade because of the extent of their negative impact on PD patients' quality of life. Although recent clinical and functional imaging studies have provided useful information, the pathophysiology of apathy and associated affective impairments remains elusive. Our aim in this review is to summarize and discuss recent advances in the development of rodent models of PD-related neuropsychiatric symptoms using neurotoxin lesion-based approaches. The data collected suggest that bilateral and partial lesions of the nigrostriatal system aimed at inducing reliable neuropsychiatric-like deficits while avoiding severe motor impairments that may interfere with behavioral evaluation, is a more selective and efficient strategy than medial forebrain bundle lesions. Moreover, of all the different classes of pharmacological agents, D2/D3 receptor agonists such as pramipexole appear to be the most efficient treatment for the wide range of behavioral deficits induced by dopaminergic lesions. Lesion-based rodent models, therefore, appear to be relevant tools for studying the pathophysiology of the non-motor symptoms of PD. Data accumulated so far confirm the causative role of dopaminergic depletion, especially in the nigrostriatal system, in the development of behavioral impairments related to apathy, depression and anxiety. They also put forward D2/D3 receptors as potential targets for the treatment of such neuropsychiatric symptoms in PD.
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: R
authors.initials: R
authors.lastname: Magnard
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Vachez
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: C
authors.initials: C
authors.lastname: Carcenac
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.|Movement Disorder Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Grenoble, France.
authors.forename: P
authors.initials: P
authors.lastname: Krack
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: O
authors.initials: O
authors.lastname: David
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: M
authors.initials: M
authors.lastname: Savasta
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Boulet
authors.affiliation: Inserm U1216, Grenoble, France.|Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Carnicella
mesh_terms: D059445:Anhedonia; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D057565:Apathy; D001522:Behavior, Animal / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D003863:Depression / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D051379:Mice; D017072:Neostriatum / Q000378:metabolism / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D000077487:Pramipexole; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077487:Pramipexole