RRC ID 46440
Author Sellings L, Pereira S, Qian C, Dixon-McDougall T, Nowak C, Zhao B, Tyndale RF, van der Kooy D.
Title Nicotine-motivated behavior in Caenorhabditis elegans requires the nicotinic acetylcholine receptor subunits acr-5 and acr-15.
Journal Eur J Neurosci
Abstract Signaling at nicotinic acetylcholine receptors in Caenorhabditis elegans controls many behaviors, including egg-laying and locomotor activity. Here, we show that C. elegans approaches a point source of nicotine in a time-, concentration- and age-dependent manner. Additionally, nicotine paired with butanone under starvation conditions prevented the reduced approach to butanone that is observed when butanone is paired with starvation alone and pairing with nicotine generates a preference for the tastes of either sodium or chloride over baseline. These results suggest nicotine acts as a rewarding substance in C. elegans. Furthermore, the nicotinic receptor antagonist mecamylamine, the smoking cessation pharmacotherapy varenicline, mutation of the dop-1 and dop-2 dopamine receptors, and mutations of either acr-5 or acr-15, two nicotinic receptor subunit genes with sequence homology to the mammalian α7 subunit, all reduced the nicotine approach behavior. These two mutants also were defective at associating the presence of nicotine with butanone under starvation conditions and acr-5 mutation could obviate the effect of pairing nicotine with salts. Furthermore, the approach deficit in acr-15 mutants was rescued by selective re-expression in a subset of neurons, but not in muscle. Caenorhabditis elegans may therefore serve as a useful model organism for nicotine-motivated behaviors that could aid in the identification of novel nicotine motivational molecular pathways and consequently the development of novel cessation aids.
Volume 37(5)
Pages 743-56
Published 2013-3-1
DOI 10.1111/ejn.12099
PMID 23351035
MeSH Age Factors Animals Behavior, Animal / drug effects* Benzazepines / pharmacology Butanones / pharmacology Caenorhabditis elegans / drug effects Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chemotaxis / drug effects Chemotaxis / genetics Chlorides / pharmacology Fasting Mecamylamine / pharmacology Muscles Mutation Neurons / metabolism Nicotine / pharmacology* Nicotinic Agonists / pharmacology Nicotinic Antagonists / pharmacology Protein Subunits / genetics Protein Subunits / metabolism* Quinoxalines / pharmacology Receptors, Dopamine D1 / genetics Receptors, Dopamine D1 / metabolism Receptors, Dopamine D2 / genetics Receptors, Dopamine D2 / metabolism Receptors, Nicotinic / genetics Receptors, Nicotinic / metabolism* Reward Sodium / pharmacology Taste Time Factors Varenicline
IF 3.115
Times Cited 12
C.elegans tm1392