A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels
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.
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.Attached Files
Accepted Version - nihms194149.pdf
Supplemental Material - 1-s2.0-S0092867406012955-mmc1.pdf
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Additional details
- PMCID
- PMC2859215
- Eprint ID
- 95471
- Resolver ID
- CaltechAUTHORS:20190514-085132111
- Howard Hughes Medical Institute (HHMI)
- NIH Predoctoral Fellowship
- T32EY017878
- NIH Predoctoral Fellowship
- T32GM008322
- NIH
- 7R01DA018341-02
- American Legacy Foundation
- University of Michigan Tobacco Research Network
- National Institute of General Medical Sciences
- National Institute on Drug Abuse
- Created
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2019-05-14Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field