QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 10, 2004, 24(45):10035-10039; doi:10.1523/JNEUROSCI.1939-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Salas, R. Articles by De Biasi, M. Search for Related Content PubMed PubMed Citation Articles by Salas, R. Articles by De Biasi, M.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Decreased Signs of Nicotine Withdrawal in Mice Null for the 4 Nicotinic Acetylcholine Receptor Subunit

Ramiro Salas, Fredalina Pieri, and Mariella De Biasi

Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

Withdrawal from chronic exposure to nicotine, the main addictive component of tobacco, produces distinctive symptoms in humans. The appearance of these symptoms is a major deterrent when people try to quit smoking. To study which type of nicotine receptor is relevant for the onset of the withdrawal syndrome, we used a mouse model of nicotine withdrawal. Wild-type mice and mice null for the 4 (4-/-) or the 2 (2-/-) nicotinic acetylcholine receptor subunits were implanted with osmotic minipumps delivering 24 mg · kg^-1 · d^-1 nicotine for 13 d. Subsequently, a single intraperitoneal injection of the nicotinic receptor antagonist mecamylamine induced behavioral symptoms of withdrawal measured as increased grooming, chewing, scratching, and shaking, plus the appearance of some unique behaviors such as jumping, leg tremors, and cage scratching. Mecamylamine injection triggered comparable withdrawal signs in wild-type and in 2-/- mice, whereas the 4-/- mice displayed significantly milder somatic symptoms. In addition, nicotine withdrawal produced hyperalgesia in wild-type but not 4-/- mice. Finally, chronic nicotine produced an increase in epibatidine binding in several areas of the brain in both wild-type and in 4-/- mice, but such receptor upregulation did not correlate with the severity of withdrawal signs.

Our results demonstrate a major role for 4-containing nicotinic acetylcholine receptors in the appearance of nicotine withdrawal symptoms. In contrast, the 2 subunit does not seem to greatly influence this phenomenon. We also show that the upregulation of epibatidine binding sites attributable to chronic nicotine, an effect associated with 2-containing receptors, is probably not related to the mechanisms underlying withdrawal.

Key words: nicotinic acetylcholine receptor; knock-out mice; 4 subunit; 2 subunit; nicotine; withdrawal

---

Received May 18, 2004; revised September 20, 2004; accepted September 20, 2004.

This article has been cited by other articles:

				K. J. Jackson, B. R. Martin, J. P. Changeux, and M. I. Damaj Differential Role of Nicotinic Acetylcholine Receptor Subunits in Physical and Affective Nicotine Withdrawal Signs J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 302 - 312. [Abstract] [Full Text] [PDF]

				M. Besson, S. Granon, M. Mameli-Engvall, I. Cloez-Tayarani, N. Maubourguet, A. Cormier, P. Cazala, V. David, J.-P. Changeux, and P. Faure Long-term effects of chronic nicotine exposure on brain nicotinic receptors PNAS, May 8, 2007; 104(19): 8155 - 8160. [Abstract] [Full Text] [PDF]

				M. Kedmi and A. Orr-Urtreger Differential brain transcriptome of {beta}4 nAChR subunit-deficient mice: is it the effect of the null mutation or the background strain? Physiol Genomics, January 17, 2007; 28(2): 213 - 222. [Abstract] [Full Text] [PDF]

				J. Wu, Q. Liu, K. Yu, J. Hu, Y.-P. Kuo, M. Segerberg, P. A. St John, and R. J. Lukas Roles of nicotinic acetylcholine receptor {beta} subunits in function of human {alpha}4-containing nicotinic receptors J. Physiol., October 1, 2006; 576(1): 103 - 118. [Abstract] [Full Text] [PDF]

				Y. Xiao, H. Fan, J. L. Musachio, Z.-L. Wei, S. K. Chellappan, A. P. Kozikowski, and K. J. Kellar Sazetidine-A, A Novel Ligand That Desensitizes {alpha}4beta2 Nicotinic Acetylcholine Receptors without Activating Them Mol. Pharmacol., October 1, 2006; 70(4): 1454 - 1460. [Abstract] [Full Text] [PDF]

				A. M. Lee and R. F. Tyndale Drugs and genotypes: how pharmacogenetic information could improve smoking cessation treatment. J Psychopharmacol, July 1, 2006; 20(4 Suppl): 7 - 14. [Abstract] [PDF]

				M. Alkondon and E. X. Albuquerque Nicotinic Receptor Subtypes in Rat Hippocampal Slices Are Differentially Sensitive to Desensitization and Early in Vivo Functional Up-Regulation by Nicotine and to Block by Bupropion J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 740 - 750. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help