Partial and full deletion of nicotinic acetylcholine receptor α4 and β2 subunits reduces sensitivity to acute nicotine administration and development of tolerance following chronic nicotine administration.

The diversity of nicotinic cholinergic receptor (nAChR) subunits underlies the complex responses to nicotine. Mice differing in the expression of α4 and β2 subunits, which are most widely expressed in brain, were evaluated for the responses to acute nicotine administration on Y-maze crossings and rears, open-field locomotion and body temperature following chronic treatment with nicotine (0, 0.25, 1.

Chronic treatment with varenicline changes expression of four nAChR binding sites in mice.

Introduction: Chronic treatment with nicotine is known to increase the α4β2-nAChR sites in brain, to decrease α6β2-nAChR sites and to have minimal effect on α3β4-and α7-nAChR populations. Varenicline is now used as a smoking cessation treatment, with and without continued smoking or nicotine replacement therapy. Varenicline, like nicotine, upregulates the α4β2-nAChR sites; however, it is not known whether varenicline treatment changes expression of the other nAChR subtypes.

Varenicline blocks β2*-nAChR-mediated response and activates β4*-nAChR-mediated responses in mice in vivo.

Introduction: The smoking cessation aid, varenicline, has higher affinity for the alpha4beta2-subtype of the nicotinic acetylcholine receptor (α4β2*-nAChR) than for other subtypes of nAChRs by in vitro assays. The mechanism of action of acute varenicline was studied in vivo to determine (a) subtype activation associated with physiological effects and (b) dose relationship as an antagonist of nicotine.

Methods: Acute doses of saline, nicotine, and varenicline were given to mice, and locomotor depression and hypothermia were measured.