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

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.