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.

Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice

“…3i) or in grooming behavior in the sucrose splash test (SST) (Supplementary Fig. 3j, k), tasks designed to evaluate behavioral depressive-like 27 and anhedonic 28 behavior, respectively. Additional control measurements showed that neither groups of mice had innate preferences for the objects used in the NOR memory test (Supplementary Fig.…”

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

“…Other studies have shown that the partial and restricted lesion (50%) of the ventrolateral area of the dorsal striatum triggered no motor deficits but increased depressive-like behavior with monoamines alterations (Tadaiesky et al, 2008;da Silva et al, 2016). Interestingly, while anhedonia-like behaviors were observed shortly after a partial bilateral 6-OHDA lesion of the dorsolateral striatum, rats exhibited depressive-like behavior later, when anhedonia was no more present, indicating a temporal dissociation between the dorsolateral striatum and the prefrontal cortex (Matheus et al, 2016). The dorsolateral part of the striatum has motor and nonmotor functions and undergoes extensive DA depletion.…”

Dopamine Circuit Mechanisms of Addiction-Like Behaviors

“…Notably, while severe PD is primarily characterized by motor impairments, patients also experience cognitive and emotional deficits that affect social behavior. As such, some ( Tadaiesky et al, 2008 ; Matheus et al, 2016 ) suggest this pathway could be critical for social impairments seen in people with SUD’s. Supporting this, in rats, nigrostriatal damage can increase depression-like symptoms and cognitive impairments in a social recognition test, as well as promote social withdrawal ( Tadaiesky et al, 2008 ; Matheus et al, 2016 ).…”