Differential cross-tolerance to the effects of nicotinic acetylcholine receptor drugs in C57BL/6J mice following chronic varenicline

This study examined the consequences of daily varenicline treatment on disruptions in operant responding (i.e. rate-decreasing effects) and hypothermia induced by administration of nicotine, epibatidine, cytisine, and cocaine in C57BL/6J mice. Furthermore, mecamylamine was used to assess the involvement of nAChRs in the effects of varenicline. Mice were trained under a fixed ratio 20 of milk reinforcement, and rectal temperatures were measured after 30 min following drug-administration. Varenicline, nicotine, epibatidine, and cytisine produced dose-dependent decreases in response rate and rectal temperature. Chronic varenicline (30 mg/kg) engendered tolerance to varenicline, but more cross-tolerance to nicotine, for both disruptions in operant responding and hypothermia. Cross-tolerance only developed to the hypothermic effects of epibatidine, and no cross-tolerance developed to any effects of cytisine and cocaine. In varenicline-tolerant mice, mecamylamine did not antagonize the effects of varenicline. The varying magnitudes of tolerance and cross-tolerance among effects and drugs are indicative of a nonuniform nAChR pharmacology in vivo.
Source: Behavioural Pharmacology - Category: Drugs & Pharmacology Tags: RESEARCH REPORTS Source Type: research