RT Journal Article
SR Electronic
T1 The Nicotinic Acetylcholine Receptor Subunit α5 Mediates Short-Term Effects of Nicotine in Vivo
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1059
OP 1066
DO 10.1124/mol.63.5.1059
VO 63
IS 5
A1 Salas, Ramiro
A1 Orr-Urtreger, Avi
A1 Broide, Ron S.
A1 Beaudet, Arthur
A1 Paylor, Richard
A1 De Biasi, Mariella
YR 2003
UL http://molpharm.aspetjournals.org/content/63/5/1059.abstract
AB 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]α-bungarotoxin 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. The American Society for Pharmacology and Experimental Therapeutics