Multiple Discriminative Stimulus Effects of the α4β2*‐Selective Agonists Ispronicline and Metanicotine

Abstract

Ispronicline and metanicotine are selective ligands at central nicotinic acetylcholine α4β2* receptors (Gao et al. Pain 2010: 149, 33; Grady et al. Neuropharmacol 2010: 58, 1054). In our study, a group of rats was trained to discriminate the stimulus properties of the nicotinic acetylcholine receptor (nAChR) agonist nicotine, and a separate group of rats was trained to discriminate the stimulus properties of the muscarinic acetylcholine receptor agonist arecoline. Ispronicline and metanicotine produced full dose‐related selection of the drug‐appropriate response option in both the nicotine‐trained and the arecoline‐trained rats. The nAChR antagonist mecamylamine blocked the discriminative stimulus effects of ispronicline and metanicotine in both groups of rats, as did the α4β2*‐selective antagonist, dihydro‐beta‐erythroidine. Neither antagonist blocked the discriminative stimulus effects of arecoline in these experiments. These data raise the possibility that ispronicline, metanicotine and similar drugs may have novel effects and require a more extensive characterization of receptor activities, through both agonists and antagonistsSupport or Funding InformationResearch supported by NIMH Grant 107499This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.