A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels.
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.
Feng
Zhaoyang
Z
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Li
Wei
W
Ward
Alex
A
Piggott
Beverly J
BJ
Larkspur
Erin R
ER
Sternberg
Paul W
PW
Xu
X Z Shawn
XZ
D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat; D001522:Behavior, Animal / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009538:Nicotine / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D050052:TRPC Cation Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D011978:Receptors, Nicotinic; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D009538:Nicotine