Chronic nicotine mitigates aberrant inhibitory motor learning induced by motor experience under dopamine deficiency

Jessica L. Koranda*, Anne C. Krok, Jian Xu, Anis Contractor, Daniel S. McGehee, Jeff A. Beeler, Xiaoxi Zhuang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.Wehave 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. β2-containing nicotinic receptors in dopamine neurons likely mediate the protective effect of cNIC against aberrant motor learning, because selective deletion of β2 nicotinic subunits in dopamine neurons reduced D2R-mediated aberrant motor learning. Finally, both cNIC treatment and β2 subunit deletion blunted postsynaptic responses toD2Rantagonism. These results suggest that a chronic decrease in function or a downregulation of β2-containing nicotinic receptors protects the striatal network against aberrant plasticity and aberrant motor learning induced by motor experience under dopamine deficiency.

Original languageEnglish (US)
Pages (from-to)5228-5240
Number of pages13
JournalJournal of Neuroscience
Volume36
Issue number19
DOIs
StatePublished - May 11 2016

Keywords

  • Aberrant plasticity
  • Beta2 nAChR
  • Dopamine D2 receptor
  • Dopamine release
  • Inhibitory learning

ASJC Scopus subject areas

  • Neuroscience(all)

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