Summary of key results obtained from studies on mice with hypersensitive nAChR subunit mutations
| nAChR Subunit and TM2 Mutation | Key Results | Reference |
|---|---|---|
| α4 | ||
| L9′S | Increased anxiety, poor motor learning, and locomotor hyperactivity in heterozygote mice | Labarca et al., 2001 |
| Sensitization to the seizure-causing action of nicotine and other nAChR agents | Fonck et al., 2003 | |
| Sensitization to the antinociceptive action of nicotine | Damaj et al., 2007 | |
| L9′A | Selective activation of α4* nAChRs is sufficient for nicotine reward, tolerance, and sensitization | Tapper et al., 2004 |
| Seizure and sleep phenotypes associated with hypersensitive α4 subunits | Fonck et al., 2005 | |
| α4* nAChRs regulate respiratory rhythm | Shao et al., 2008 | |
| Demonstrated strong expression of α4* nAChRs in ventrolateral medial habenula | Fonck et al., 2009 | |
| Selective activation of α4* nAChRs is necessary and sufficient for varenicline's ability to reduce alcohol consumption | Hendrickson et al., 2010 | |
| α6 | ||
| L9′S | Selective α6* nAChR activation causes spontaneous and nicotine-elicited locomotor hyperactivity | Drenan et al., 2008 |
| Altered frequency-dependent DA release in α6 L9′S mice; α4 subunits are required for all significant behavioral effects of the α6 L9′S mutation | Drenan et al., 2010 | |
| Voluntary exercise is inversely correlated with the degree of α6* nAChR hypersensitivity | Cohen et al., 2012 | |
| α7 | ||
| L250T | Perinatal death of α7 L250T homozygotes but survival of L250T heterozygotes | Orr-Urtreger et al., 2000 |
| Hypersensitivity to nicotine-induced seizures | Broide et al., 2002 | |
| Somatodendritic expression of α7 nAChRs on midbrain DA neurons | Wooltorton et al., 2003 | |
| α9 | ||
| L9′T | Mutant mice are protected from hearing loss in response to intense noise | Taranda et al., 2009 |