RT Journal Article SR Electronic T1 METHAMPHETAMINE-LIKE DISCRIMINATIVE-STIMULUS EFFECTS OF NICOTINIC AGONISTS JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.113.211235 DO 10.1124/jpet.113.211235 A1 Rajeev I Desai A1 Jack Bergman YR 2014 UL http://jpet.aspetjournals.org/content/early/2014/01/03/jpet.113.211235.abstract AB Nicotine recently was shown to engender methamphetamine (MA)-like discriminative-stimulus effects in rats, which may be indicative of shared psychomotor stimulant properties. To further investigate such overlapping discriminative-stimulus effects, nicotinic agonists varying in efficacy and selectivity were studied in squirrel monkeys that discriminated a moderate i.m. dose of MA (0.1 mg/kg) from vehicle. These included α4β2-selective ligands that may vary in efficacy from relatively high [nicotine, (+)- and (-)-epibatidine] to relatively low [isoarecolone, varenicline, (-)-cytisine, (-)-lobeline] and the α7-selective ligands anabaseine and anabasine. 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) or did not [(-)-cytisine and (-)-lobeline] substitute for MA. The relative potencies of nicotinic agonists, based on ED50 values, corresponded better with their relative affinities at α4β2 than α7 receptors. Regardless of selectivity or efficacy, nicotinic agonists also were observed to produce untoward effects including salivation and emesis during or after experimental sessions. In pretreatment studies, the α4β2-selective antagonist dihydro-β-erythroidine hydrobromide (DHβE: 0.032 and 0.1 mg/kg) and the partial agonists varenicline (0.0032–0.1 mg/kg) and (-)-cytisine (0.032 and 0.1 mg/kg) surmountably antagonized (>10-fold rightward shift) nicotine's MA-like effects but were ineffective in blocking nicotine's emetic effects. Overall, our results show that: 1) MA-like discriminative-stimulus effects of nicotinic agonists likely are mediated through α4β2 nAChR actions and 2) nicotinic α4β2 partial agonists, like the nicotinic antagonist DHβE, can reduce MA-like behavioral effects of nicotine.