Effects of varenicline on the discriminative stimulus effects of nicotine in female cynomolgus monkeys

Abstract

Nicotine (NIC) is a widely abused drug, primarily consumed through tobacco products. Varenicline (VAR), a nicotinic acetylcholine receptor partial agonist, is an FDA‐approved pharmacotherapy for smoking cessation. Despite its clinical use, little preclinical research exists to understand how VAR reduces the abuse liability of NIC. Though VAR purportedly reduces the reinforcing effects of NIC, the effects of VAR on the subjective effects associated with NIC are not conclusive. To examine this relationship, we investigated the effects of VAR alone and in combination with NIC in a two‐choice, food‐reinforced, drug discrimination procedure in which ovariectomized female cynomolgus monkeys (n=4) were trained to discriminate 0.3 mg/kg (base) NIC from saline (i.m., 10‐min presession). Preliminary data suggest that VAR (0.03–0.3 mg/kg, base, i.m., 10‐min presession) does not engender NIC‐like discriminative stimulus effects when substituted for NIC, nor affect response rates. When administered 10 min prior to NIC, VAR (0.1–0.3 mg/kg, i.m.) potentiated the rate‐decreasing effects of NIC without affecting discrimination; however, VAR blocked the NIC‐like discriminative stimulus effects when administered 2 hours prior to the training dose of NIC. These results suggest VAR has biphasic effects – initially interacting in a synergistic manner with NIC, but antagonizing NIC at later time points. DA12460