Guanosine prevents depressive-like behaviors in rats following bilateral dorsolateral striatum lesion induced by 6-hydroxydopamine.

Abstract:

:The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). Beyond the nigrostriatal pathway, dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC) and hippocampus, which have been associated with the appearance of anhedonia and depression at pre-motor phases of PD. Herein, using behavioral and biochemical approaches, we investigated the protective effects of guanosine (GUO) (7.5 mg/kg, i.p.) against emotional impairments and cellular events in cortical, striatal and hippocampal slices of rats submitted to a bilateral infusion of 6-OHDA (10 μg/hemisphere) into the DLS. 6-OHDA-lesioned rats displayed anhedonic- and depressive-like behaviors addressed in the splash and forced swimming tests (at 8 and 21 days after lesion, respectively). In addition, no alterations in motor performance in the open field test and social interaction were observed. Biochemical analyses were performed 22 days after 6-OHDA lesions. 6-OHDA lesion induced hippocampal mitochondrial membrane potential disruption. However, intra-striatal 6-OHDA administration did not alter the ROS levels measured in cortical, striatal and hippocampal slices. GUO treatment attenuated anhedonic- and depressive-like behaviors in 6-OHDA-lesioned rats and protected hippocampal slices against the mitochondrial membrane potential disruption. These results indicate antidepressant-like effects of GUO in a rat model of PD, indicating the potential of GUO for the treatment of depression associated with PD.

journal_name

Behav Brain Res

authors

Marques NF,Binder LB,Roversi K,Sampaio TB,Constantino LC,Prediger RD,Tasca CI

doi

10.1016/j.bbr.2019.112014

subject

Has Abstract

pub_date

2019-10-17 00:00:00

pages

112014

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(19)30294-3

journal_volume

372

pub_type

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