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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the alpha6 subunit.

In male rats continually self-administering nicotine (approximately 1.5 mg free base/kg/day), we found a significant increase of nicotinic acetylcholine receptors (nAChRs) labeled by epibatidine (Epb) in 11 brain areas. A large increase of high-affinity Epb binding sites was apparent in the ventral tegmentum/substantia nigra, nucleus tractus solitarii, nucleus accumbens, thalamus/subthalamus, parietal cortex, hypothalamus, and amygdala. A smaller but significant up-regulation of high-affinity Epb sites was seen in the piriform cortex, hippocampus, caudate/putamen, and cerebellar cortex. The up-regulation of nAChRs, shown by immunoadsorption and Western blotting, involved alpha4, alpha6, and beta2 subunits. As a consequence of long-term self-administration of nicotine, the alpha6 immunoreactive (IR) binding of either labeled Epb or 125I-alpha-conotoxin MII increased to a much greater extent than did alpha4 or beta2 IR binding of Epb. In addition, the beta2 IR binding of Epb was consistently enhanced to a greater extent than was alpha4. These findings may reflect a larger surface membrane retention of alpha6-containing and, to some degree, beta2-containing nAChRs compared with alpha4-containing nAChRs during long-term self-administration of nicotine.[1]

References

  1. Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the alpha6 subunit. Parker, S.L., Fu, Y., McAllen, K., Luo, J., McIntosh, J.M., Lindstrom, J.M., Sharp, B.M. Mol. Pharmacol. (2004) [Pubmed]
 
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