title: Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.
abstract: The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). The nigrostriatal dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC), which has been associated with the appearance of anhedonia and depression at pre-motor phases of PD. Using behavioral, neurochemical, and electrophysiological approaches, we investigated the temporal dissociation between the role of the DLS and PFC in the appearance of anhedonia and defense behaviors relevant to depression in rats submitted to bilateral DLS lesions with 6-hydroxydopamine (6-OHDA; 10 μg/hemisphere). 6-OHDA induced partial dopaminergic nigrostriatal damage with no gross motor impairments. Anhedonic-like behaviors were observed in the splash and sucrose consumption tests only 7 days after 6-OHDA lesion. By contrast, defense behaviors relevant to depression evaluated in the forced swimming test and social withdrawal only emerged 21 days after 6-OHDA lesion when anhedonia was no longer present. These temporally dissociated behavioral alterations were coupled to temporal- and structure-dependent alterations in dopaminergic markers such as dopamine D1 and D2 receptors and dopamine transporter, leading to altered dopamine sensitivity in DLS and PFC circuits, evaluated electrophysiologically. These results provide the first demonstration of a dissociated involvement of the DLS and PFC in anhedonic-like and defense behaviors relevant to depression in 6-OHDA-lesioned rats, which was linked with temporal fluctuations in dopaminergic receptor density, leading to altered dopaminergic system sensitivity in these two brain structures. This sheds new light to the duality between depressive and anhedonic symptoms in PD.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.
authors.forename: Filipe C
authors.initials: FC
authors.lastname: Matheus
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.|Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rial
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Joana I
authors.initials: JI
authors.lastname: Real
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemos
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Takahashi
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Bertoglio
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, 3005-504, Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil. ruidsp@hotmail.com.
authors.forename: Rui D
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D059445:Anhedonia; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003863:Depression / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D008297:Male; D009043:Motor Activity; D016627:Oxidopamine; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Anhedonia; Depression; Dorsolateral striatum; Parkinson’s disease; Pre-frontal cortex; Social isolation