The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo.
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 alpha and three beta subunits. To study the physiological role of the alpha 5 subunit, we have generated alpha 5-deficient mice. These mice have a generally healthy appearance and are normal in a standard battery of behavioral tests. However, the sensitivity of alpha 5 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 alpha 4, alpha 6, alpha 7, beta 2, and beta 4. In addition, (125)I-epibatidine and [(125)I]alpha-bungarotoxin binding in the brains of alpha 5-deficient mice is normal. Together, these results suggest a direct involvement of the alpha 5 subunit in the observed phenotypes.
Salas
Ramiro
R
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Orr-Urtreger
Avi
A
Broide
Ron S
RS
Beaudet
Arthur
A
Paylor
Richard
R
De Biasi
Mariella
M
D000818:Animals; D029721:Drosophila Proteins; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009538:Nicotine / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D029721:Drosophila Proteins; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C113681:nicotinic acetylcholine receptor alpha-subunits, Drosophila; D009538:Nicotine