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Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the alpha6 subunit.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Parker, Steven L. Fu, Yitong McAllen, Kathleen Luo, Jianhong McIntosh, J. Michael Lindstrom, Jon M. Sharp, Burt M. |
| Copyright Year | 2004 |
| Abstract | 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1124/mol.65.3.611 |
| PubMed reference number | 14978239 |
| Journal | Medline |
| Volume Number | 65 |
| Issue Number | 3 |
| Alternate Webpage(s) | http://molpharm.aspetjournals.org/content/molpharm/65/3/611.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1124/mol.65.3.611 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |