Chronic nicotine selectively enhances α4β2* nicotinic acetylcholine receptors in the nigrostriatal dopamine pathway

Cheng Xiao, Raad Nashmi, Sheri McKinney, Haijiang Cai, J. Michael McIntosh, Henry A. Lester

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


These electrophysiological experiments, in slices and intact animals, study the effects of in vivo chronic exposure to nicotine on functional α4β2* nAChRs in the nigrostriatal dopaminergic (DA) pathway. Recordings were made in wild-type and α4 nicotinic acetylcholine receptor (nAChR) subunit knock-out mice. Chronic nicotine enhanced methyllycaconitine citrate hydrate-resistant, dihydro-β-erythroidine hydrobromide-sensitive nicotinic currents elicited by 3-1000 μM ACh in GABAergic neurons of the substantia nigra pars reticulata (SNr), but not in DA neurons of the substantia nigra pars compacta (SNc). This enhancement leads to higher firing rates of SNr GABAergic neurons and consequently to increased GABAergic inhibition of the SNc DA neurons. In the dorsal striatum, functional α4* nAChRs were not found on the neuronal somata; however, nicotine acts via α4β2* nAChRs in the DA terminals to modulate glutamate release onto the medium spiny neurons. Chronic nicotine also increased the number and/or function of these α4β2* nAChRs. These data suggest that in nigrostriatal DA pathway, chronic nicotine enhancement of α4β2* nAChRs displays selectivity in cell type and in nAChR subtype as well as in cellular compartment. These selective events augment inhibition of SNcDAneurons by SNr GABAergic neurons and also temper the release of glutamate in the dorsal striatum. The effects may reduce the risk of excitotoxicity in SNc DA neurons and may also counteract the increased effectiveness of corticostriatal glutamatergic inputs during degeneration of theDAsystem. These processes may contribute to the inverse correlation between tobacco use and Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)12428-12439
Number of pages12
JournalJournal of Neuroscience
Issue number40
StatePublished - Oct 7 2009
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Chronic nicotine selectively enhances α4β2* nicotinic acetylcholine receptors in the nigrostriatal dopamine pathway'. Together they form a unique fingerprint.

Cite this