Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina.
Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine's beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions.
Department of Biology, West Chester University, West Chester, PA, United States.
Daniel J
DJ
Bach
Department of Biology, West Chester University, West Chester, PA, United States.
Matthew
M
Tenaglia
Department of Biology, West Chester University, West Chester, PA, United States.
Debra L
DL
Baker
Department of Biology, West Chester University, West Chester, PA, United States.
Sean
S
Deats
Department of Biology, West Chester University, West Chester, PA, United States.
Erica
E
Montgomery
Department of Biology, West Chester University, West Chester, PA, United States. Electronic address: opagan@wcupa.edu.
Oné R
OR
Pagán
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001665:Binding Sites; D003367:Cotinine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010932:Planarians / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000378:metabolism
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D003367:Cotinine
Artificial pond water; Cotinine; Motility; Nicotine; Planaria; Seizure-like movements; Withdrawal