Nicotine recently was shown to engender methamphetamine (MA)-like discriminative stimulus. To investigate overlapping discriminative-stimulus effects, nicotinic agonists varying in efficacy and selectivity were studied in squirrel monkeys that discriminated a moderate intramuscular dose of MA from vehicle. Results show that nicotine, (+)-epibatidine, and (−)-epibatidine substituted fully for MA, whereas the highest doses of other nicotinic agonists produced intermediate levels of MA-like effects (isoarecolone, anabaseine, anabasine, and varenicline). The relative potencies of nicotinic agonists, based on ED50 values, corresponded better with their relative affinities at α4β2 than α7 receptors. In pretreatment studies, α4β2-selective antagonist and the partial agonists antagonized nicotine’s MA-like effects. Overall, our results show that: 1) MA-like discriminative-stimulus effects of nicotinic agonists are mediated through α4β2 nAChR actions and 2) nicotinic α4β2 partial agonists can reduce MA-like behavioral effects of nicotine.
See article at J Pharmacol Exp Ther 2014, 348:478–488.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics