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A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels

Feng, Zhaoyang and Li, Wei and Ward, Alex and Piggott, Beverly J. and Larkspur, Erin R. and Sternberg, Paul W. and Xu, X. Z. Shawn (2006) A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels. Cell, 127 (3). pp. 621-633. ISSN 0092-8674. PMCID PMC2859215. https://resolver.caltech.edu/CaltechAUTHORS:20190514-085132111

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Abstract

Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.cell.2006.09.035DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859215PubMed CentralArticle
ORCID:
AuthorORCID
Li, Wei0000-0003-2543-2558
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2006 Elsevier Inc. Received 21 November 2005, Revised 16 July 2006, Accepted 15 September 2006, Available online 2 November 2006. We thank William Schafer, Gary Schindelman, Patrick Hu, Raad Nashmi, and Craig Montell for comments and advice; Junichi Nakai for the G-CaMP plasmid; Millet Treinin for the deg-3 strain; Henry Lester for mouse nAChR cDNA plasmids; and Barbara Perry and Rahul Mahapatra for technical assistance. Z.F. was inspired to study nicotine by previous training with W.S. Some strains were obtained from the CGC and C. elegans Gene Knockout Consortium. P.W.S. is an HHMI investigator. This work was supported by USPHS training grants T32EY017878 (A.W.) and T32GM008322 (B.J.P.), the Howard Hughes Medical Institute (HHMI) (P.W.S.), NIDA grant 7R01DA018341-02 (P.W.S.), the University of Michigan BSSP program (X.Z.S.X.), and grants from the American Legacy Foundation via UMTRN and NIGMS (X.Z.S.X.). Z.F. and X.Z.S.X. conceived and designed the experiments. Z.F. and W.L. performed the experiments and analyzed the data. A.W., B.J.P., and E.R.L. helped perform some experiments and paper writing. P.W.S. contributed critical reagents, intellectual input, and help with paper writing. X.Z.S.X. and Z.F. wrote the paper.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIH Predoctoral FellowshipT32EY017878
NIH Predoctoral FellowshipT32GM008322
NIH7R01DA018341-02
American Legacy FoundationUNSPECIFIED
University of Michigan Tobacco Research NetworkUNSPECIFIED
National Institute of General Medical SciencesUNSPECIFIED
National Institute on Drug AbuseUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC2859215
Record Number:CaltechAUTHORS:20190514-085132111
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190514-085132111
Official Citation:Zhaoyang Feng, Wei Li, Alex Ward, Beverly J. Piggott, Erin R. Larkspur, Paul W. Sternberg, X.Z. Shawn Xu, A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels, Cell, Volume 127, Issue 3, 2006, Pages 621-633, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2006.09.035. (http://www.sciencedirect.com/science/article/pii/S0092867406012955)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95471
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 May 2019 21:12
Last Modified:15 Nov 2019 18:40

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