Behavioral effects of 6-hydroxydopamine-induced damage to nigro-striatal pathway and Locus coeruleus as a rodent model of Parkinson's disease

Behav Brain Res. 2024 Jan 23;462:114873. doi: 10.1016/j.bbr.2024.114873. Online ahead of print.ABSTRACTParkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc), which leads to motor and non-motor symptoms (NMS). NMS can appear many years before the classical motor symptoms and are associated with the neurodegeneration of several nuclei; in this work, we highlight the neurodegeneration of Locus coeruleus (LC) in PD. The aim was to investigate the effects of depleting SNpc and LC catecholaminergic neurons on behavioral and neurobiological endpoints. Here we used 6-hydroxydopamine (6-OHDA) in order to induced neurotoxic damage in three independent experimental groups: SNpc lesion group, which 6-OHDA was injected into CPu (CPu-6-OHDA), LC lesion group, which 6-OHDA was injected directly on LC to selectively caused a damage on this nucleus (LC-6-OHDA), and the combined SNpc and LC lesion group (CL-6-OHDA). Next, the behavioral studies were performed using the Morris water maze (MWM), open field (OF), and elevated plus maze (EPM). After stereotaxic surgeries, the animals showed a loss of 67% and 77% of Tyrosine hydroxylase (TH) reactive neurons in the SNpc and LC, respectively. The behavioral analysis showed the anxiety-like behavior in CL-6-OHDA group in the EPM test; in the MWM test, the combined lesions (CL-6-OHDA) showed an impairment in memory acquisition and ...
Source: Behavioural Brain Research - Category: Neurology Authors: Source Type: research