Differential effects of activating D1 and D2 receptors on electrophysiology of neostriatal neurons in a rat model of Parkinson's disease induced by paraquat and maneb

• Published in: Neuroscience research Vol. 71; no. 4; pp. 411 - 420
• Main Authors: Xu, Haiyan, Chen, Ruirui, Cai, Xiaoyan, He, Defu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.12.2011
• Subjects: Animals; Disease Models, Animal; Dopamine receptors; Electrophysiological Phenomena; Electrophysiology; Fungicides, Industrial - toxicity; Herbicides - toxicity; In vivo; Male; Maneb - toxicity; Neocortex - metabolism; Neostriatum; Paraquat - toxicity; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Electrophysiology; In vivo; Parkinson's disease; Neostriatum; Dopamine receptors
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2011.08.011

► Exposure of PQ and MB induced Parkinsonism and neuronal loss of SNc in rats. ► Electrophysiology of neostriatum was compared between exposed rats and controls. ► We observed increase of firing activity of neostriatal neurons in exposed rats. ► Stronger inhibitory effects of activating D1 were found on neostriatal neurons. ► However activating D2 receptors caused weaker excitatory effects in exposed rats. Neostriatum plays an important role in the pathophysiology of Parkinson's disease (PD). However, the changes of sensitivity of dopamine receptors of neostriatal neurons in PD have been less addressed in vivo. In the present study, systemic exposure to paraquat and maneb induced Parkinsonian symptoms and neuronal loss of substantia nigra pars compacta. Using single-unit recording methods, three types of neostriatal neurons were recorded including medium spiny-like neurons, large aspiny-like neurons and fast-spiking interneurons. In the exposed rats, increased firing activity of neostriatal neurons was revealed when compared to control rats. Following D1 receptor agonist, SKF38393 and D2 receptor agonist, LY171555 iontophoretically administrated respectively, effects of increase and decrease in firing activity were both observed in neostriatal neurons. However, stronger inhibitory effects of activating D1 receptors and weaker excitatory effects of activating D2 receptors were found in the exposed rats as compared to controls. It indicated that differential changes of sensitivity of D1 and D2 receptors in Parkinson's disease were related to the modulation of the imbalance between D1-receptor-dependent striatonigral direct pathway and D2-receptor-dependent striatopallidal indirect pathway. Our results illustrate the electrophysiological changes of in vivo neostriatal neurons in Parkinson's disease, thereby providing insight into the regulatory mechanisms of dopamine-mediated physiology.