The nicotinic acetylcholine receptor subunit α5 mediates short-term effects of nicotine in vivo

Ramiro Salas, Avi Orr-Urtreger, Ron S. Broide, Arthur Beaudet, Richard Paylor, Mariella De Biasi

Research output: Contribution to journalArticlepeer-review

Abstract

Nicotine, acting at pentameric neuronal nicotinic acetylcholine receptors (nAChRs), is the primary addictive component in tobacco. At low doses, it affects attention, learning, memory, anxiety, cardiovascular responses, thermoregulation, and nociception. At high doses, nicotine produces more drastic behaviors and eventually induces tonic-clonic seizures in rodents. In mammals, several subunits of the nAChRs have been cloned, including eight α and three β subunits. To study the physiological role of the α5 subunit, we have generated α5-deficient mice. These mice have a generally healthy appearance and are normal in a standard battery of behavioral tests. However, the sensitivity of α5 mutant mice to nicotine-induced behaviors and seizures is dramatically reduced compared with their wild-type littermates. These animals have a normal brain anatomy and normal levels of mRNA for other nAChR subunits, namely α4, α6, α7, β2, and β4. In addition, 125I-epibatidine and [125I]αbungarotoxin binding in the brains of α5-deficient mice is normal. Together, these results suggest a direct involvement of the α5 subunit in the observed phenotypes.

Original languageEnglish
Pages (from-to)1059-1066
Number of pages8
JournalMolecular Pharmacology
Volume63
Issue number5
DOIs
StatePublished - 1 May 2003
Externally publishedYes

Fingerprint

Dive into the research topics of 'The nicotinic acetylcholine receptor subunit α5 mediates short-term effects of nicotine in vivo'. Together they form a unique fingerprint.

Cite this