Publication Date:
2004-11-06
Description:
The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with a4 nicotinic subunits containing a single point mutation, Leu9' --〉 Ala9' in the pore-forming M2 domain, rendering a4* receptors hypersensitive to nicotine. Selective activation of a4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of a4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tapper, Andrew R -- McKinney, Sheri L -- Nashmi, Raad -- Schwarz, Johannes -- Deshpande, Purnima -- Labarca, Cesar -- Whiteaker, Paul -- Marks, Michael J -- Collins, Allan C -- Lester, Henry A -- DA-15663/DA/NIDA NIH HHS/ -- DA-3194/DA/NIDA NIH HHS/ -- MH-49716/MH/NIMH NIH HHS/ -- NS-11756/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 5;306(5698):1029-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528443" target="_blank"〉PubMed〈/a〉
Keywords:
Alkaloids/metabolism
;
Animals
;
Azocines/metabolism
;
Bicyclo Compounds, Heterocyclic/metabolism
;
Brain/drug effects/metabolism
;
Calcium/metabolism
;
Cells, Cultured
;
*Drug Tolerance
;
Leucine
;
Mice
;
Mice, Inbred C57BL
;
Motor Activity/drug effects
;
Neurons/metabolism
;
Nicotine/*pharmacology
;
Point Mutation
;
Pyridines/metabolism
;
Quinolizines/metabolism
;
Receptors, Nicotinic/genetics/*physiology
;
*Reward
;
Serine
;
Tobacco Use Disorder/*metabolism
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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