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

• Published in: Behavioural brain research Vol. 372; p. 112014
• Main Authors: Marques, Naiani Ferreira, Binder, Luisa Bandeira, Roversi, Katiane, Sampaio, Tuane Bazanella, Constantino, Leandra Celso, Prediger, Rui Daniel, Tasca, Carla Inês
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17.10.2019
• Subjects: Anhedonia; Depression; Dorsolateral striatum; Guanosine; Parkinson’s disease; Dorsolateral striatum; Depression; Anhedonia; Guanosine; Parkinson’s disease
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2019.112014

•GUO attenuated anhedonic-like behavior in the splash test in 6-OHDA-lesioned rats.•GUO promoted an antidepressant-like effect in the FST in 6-OHDA-treated rats.•Rat intra-striatal 6-OHDA cause no alterations in motor performance.•6-OHDA did not alter ROS levels in rat cortical, striatal and hippocampal slices.•GUO prevented 6-OHDA-evoked mitochondrial potential disruption in hippocampal slices. 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.