Characterization of Cholinergic Receptor Agonists Nicotine and Arecoline Using Drug Discrimination
Bresnahan, Kelly M.
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Smoking is the leading cause of preventable death worldwide partly due to the addictive properties of nicotine. Moreover, nicotine’s discriminative stimulus property makes it easy to relapse after smoking cessation. In this study, the discriminative stimulus property of nicotine was examined by using the two-key and three-key drug discrimination paradigms. Two-key discrimination required training rats to discriminate between nicotine and saline or arecoline- another acetylcholine (ACh) receptor agonist- and saline while three-key discrimination required rats to discriminate between nicotine, arecoline, and saline. Two-key discrimination tests performed on two sets of six rats showed that nicotine does not generalize to arecoline while arecoline may generalize to nicotine at high doses. Varenicline and carbachol were also tested in this two-key discrimination paradigm and the results concur with previous findings that they are a nicotinic partial agonist and a muscarinic agonist, respectively. These results also suggest that arecoline may be a muscarinic and nicotinic agonist at high doses while nicotine is solely a nicotinic agonist. A relatively new method of drug discrimination, three-key discrimination, was studied. While still in the initial stages, preliminary findings with three-key discrimination support the validity of the method.