Abstract
It has been suggested that the negative effects associated with nicotine withdrawal promote continued tobacco use and contribute to the high relapse rate of smoking behaviors. Thus, it is important to understand the receptor-mediated mechanisms underlying nicotine withdrawal to aid in the development of more successful smoking cessation therapies. The effects of nicotine withdrawal are mediated through nicotinic acetylcholine receptors (nAChRs); however, the role of nAChRs in nicotine withdrawal remains unclear. Therefore, we used mecamylamine-precipitated, spontaneous, and conditioned place aversion (CPA) withdrawal models to measure physical and affective signs of nicotine withdrawal in various nAChR knockout (KO) mice. β2, α7, and α5 nAChR KO mice were chronically exposed to nicotine through surgically implanted osmotic minipumps. Our results show a loss of anxiety-related behavior and a loss of aversion in the CPA model in β2 KO mice, whereas α7 and α5 KO mice displayed a loss of nicotine withdrawal-induced hyperalgesia and a reduction in somatic signs, respectively. These results suggest that β2-containing nAChRs are involved in the affective signs of nicotine withdrawal, whereas non-β2-containing nAChRs are more closely associated with physical signs of nicotine withdrawal; thus, the nAChR subtype composition may play an important role in the involvement of specific subtypes in nicotine withdrawal.
Footnotes
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This study was supported by the National Institute on Drug Abuse (Grants DA-12610 and DA-05274).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.132977.
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ABBREVIATIONS: nAChR, nicotinic acetylcholine receptor; CPA, conditioned place aversion; KO, knockout; WT, wild type; sal, saline; mec, mecamylamine; nic, nicotine.
- Received October 12, 2007.
- Accepted January 8, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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