Further exploring cognitive and affective outcomes following bilateral 6- hydroxidopamine infusion into the substance nigra or striatum of rats

Abstract The majority of animal models of PD focus on the motor symptoms induced by unilateral injections of neurotoxins such as 6-hydroxidopamine (6-OHDA) in the nigrostriatal dopaminergic pathways. However, motor changes induced by unilateral 6-OHDA injections may interfere in the identification of cognitive and affective dysfunctions. To select an appropriate method for studying non-motor symptoms of PD and potential neuroprotective treatments, the present study aimed to compare the behavioral effects of bilateral 6-OHDA infusion directly into the SNpc or striatum of rats. A battery of behavioral tests including affective and cognitive tasks was conducted for 22 days after nigrostriatal lesions. 6-OHDA infusion into the SNpc resulted in the elevated mortality rate of rats over time while no significant effect was detected in rats that received 6-OHDA into the striatum. A massive degeneration of TH-IR neurons was observed in the SNpc, striatum, and VTA with either 6-OHDA infusion into the SNpc or the striatum. Concerning functional outcomes, 6-OHDA infusion into the striatum resulted in a decrease in the general exploratory activity 7 days after lesion. Rats receiving 6-OHDA into the SNpc showed cognitive impairments and despair-like behaviors. A decreased number of newborn neurons was found in the hippocampus of rats that received the toxin in the striatum, indicating decreased neurogenesis. Both 6-OHDA infusion into the SNpc or into the striatum impacted the maturation of hippocampal newborn neurons. These results indicate that bilateral injections into the SNpc might be a proper method to study the non-motor symptoms of PD.