Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.
Mol Neurobiol. 2015-07-12; 53(6): 3891-3899
DOI: 10.1007/s12035-015-9330-z
Lire sur PubMed
Matheus FC(1), Rial D(1)(2), Real JI(2), Lemos C(2), Takahashi RN(1), Bertoglio LJ(1), Cunha RA(2)(3), Prediger RD(4).
Author information:
(1)Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.
(2)Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517, Coimbra, Portugal.
(3)Faculty of Medicine, University of Coimbra, 3005-504, Coimbra, Portugal.
(4)Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.
.
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.