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Molecular Pharmacology

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Research ArticleArticle

Up-Regulation of Brain Nicotinic Acetylcholine Receptors in the Rat during Long-Term Self-Administration of Nicotine: Disproportionate Increase of the α6 Subunit

Steven L. Parker, Yitong Fu, Kathleen McAllen, Jianhong Luo, J. Michael McIntosh, Jon M. Lindstrom and Burt M. Sharp
Molecular Pharmacology March 2004, 65 (3) 611-622; DOI: https://doi.org/10.1124/mol.65.3.611
Steven L. Parker
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Yitong Fu
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Kathleen McAllen
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Jianhong Luo
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J. Michael McIntosh
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Jon M. Lindstrom
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This article has a correction. Please see:

  • Correction to “Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the α6 subunit” - April 01, 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 α4, α6, and β2 subunits. As a consequence of long-term self-administration of nicotine, the α6 immunoreactive (IR) binding of either labeled Epb or 125I-α-conotoxin MII increased to a much greater extent than did α4 or β2 IR binding of Epb. In addition, the β2 IR binding of Epb was consistently enhanced to a greater extent than was α4. These findings may reflect a larger surface membrane retention of α6-containing and, to some degree, β2-containing nAChRs compared with α4-containing nAChRs during long-term self-administration of nicotine.

  • Received August 19, 2003.
  • Accepted November 13, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 65 (3)
Molecular Pharmacology
Vol. 65, Issue 3
1 Mar 2004
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Research ArticleArticle

Up-Regulation of Brain Nicotinic Acetylcholine Receptors in the Rat during Long-Term Self-Administration of Nicotine: Disproportionate Increase of the α6 Subunit

Steven L. Parker, Yitong Fu, Kathleen McAllen, Jianhong Luo, J. Michael McIntosh, Jon M. Lindstrom and Burt M. Sharp
Molecular Pharmacology March 1, 2004, 65 (3) 611-622; DOI: https://doi.org/10.1124/mol.65.3.611

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Research ArticleArticle

Up-Regulation of Brain Nicotinic Acetylcholine Receptors in the Rat during Long-Term Self-Administration of Nicotine: Disproportionate Increase of the α6 Subunit

Steven L. Parker, Yitong Fu, Kathleen McAllen, Jianhong Luo, J. Michael McIntosh, Jon M. Lindstrom and Burt M. Sharp
Molecular Pharmacology March 1, 2004, 65 (3) 611-622; DOI: https://doi.org/10.1124/mol.65.3.611
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