TY - JOUR
T1 - The nicotinic acetylcholine receptor subunit α5 mediates short-term effects of nicotine in vivo
AU - Salas, Ramiro
AU - Orr-Urtreger, Avi
AU - Broide, Ron S.
AU - Beaudet, Arthur
AU - Paylor, Richard
AU - De Biasi, Mariella
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
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]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.
UR - http://www.scopus.com/inward/record.url?scp=0037731430&partnerID=8YFLogxK
U2 - 10.1124/mol.63.5.1059
DO - 10.1124/mol.63.5.1059
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C2 - 12695534
AN - SCOPUS:0037731430
SN - 0026-895X
VL - 63
SP - 1059
EP - 1066
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 5
ER -