期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 19, 页码 5228-5240出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2754-15.2016
关键词
aberrant plasticity; Beta2 nAChR; dopamine D2 receptor; dopamine release; inhibitory learning
资金
- National Institutes of Health [DA25875]
- National Institutes of Health (National Institute of Neurological Disorders and Stroke) [R21NS083383, 5R01MH099114]
Although dopamine receptor antagonism has long been associated with impairments in motor performance, more recent studies have shown that dopamine D2 receptor (D2R) antagonism, paired with a motor task, not only impairs motor performance concomitant with the pharmacodynamics of the drug, but also impairs future motor performance once antagonism has been relieved. We have termed this phenomenon aberrant motor learning and have suggested that it may contribute to motor symptoms in movement disorders such as Parkinson's disease (PD). Here, we show that chronic nicotine (cNIC), but not acute nicotine, treatment mitigates the acquisition of D2R-antagonist-induced aberrant motor learning in mice. Although cNIC mitigates D2R-mediated aberrant motor learning, cNIC has no effect on D1R-mediated motor learning. beta 2-containing nicotinic receptors in dopamine neurons likely mediate the protective effect of cNIC against aberrant motor learning, because selective deletion of beta 2 nicotinic subunits in dopamine neurons reduced D2R-mediated aberrant motor learning. Finally, both cNIC treatment and beta 2 subunit deletion blunted postsynaptic responses to D2R antagonism. These results suggest that a chronic decrease in function or a downregulation of beta 2-containing nicotinic receptors protects the striatal network against aberrant plasticity and aberrant motor learning induced by motor experience under dopamine deficiency.
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