Rapid nicotine tolerance and cross-tolerance to varenicline in rhesus monkeys: Drug discrimination.

ABSTRACT: Acute tolerance to effects of nicotine plays an important role in nicotine dependence, but the mechanism underlying these effects is unclear. Drug discrimination was used in the current study to examine the impact of nicotine pretreatment on sensitivity to the discriminative stimulus effects of nicotine and the FDA-approved smoking cessation pharmacotherapy varenicline. Rhesus monkeys (n = 4) discriminated 0.032 mg/kg nicotine base iv from saline under an FR5 schedule of stimulus-shock termination. Both nicotine and varenicline increased drug-appropriate responding; ED50 values (95% confidence limits) were 0.0087 [0.0025, 0.030] and 0.028 [0.0096, 0.082] mg/kg, respectively. Additional pretreatment injections of the training dose of nicotine (0.032 mg/kg, iv) produced tolerance to i

SUBMITTER: Moerke MJ 

PROVIDER: S-EPMC6792293 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature