Nicotine Self-Administration as Paradigm for Medication Discovery for Smoking Cessation: Recent Findings in Medications Targeting the Cholinergic System.

Abstract

Tobacco kills every year approximately six million people as a direct result of direct use, and it is still considered one of the most excruciating threats for human health worldwide. The low successful rates of the currently available pharmacotherapies to assist in quitting tobacco use suggest there is a need for more effective treatments.The intravenous self-administration (IVSA) paradigm is considered the gold standard to study voluntary drug intake in animal models, including nicotine. The IVSA paradigm has been used to identify key mechanisms involved in the addictive properties of nicotine in both rodents and nonhuman primates. In this chapter we describe how the IVSA paradigm has served to further investigate the role of nicotinic acetylcholine receptors (nAChRs) in the reinforcing properties of nicotine. Notably, this review will cover recent advances (i.e., research carried out during the past decade) using the IVSA paradigm, with a focus on the status of research on current smoking cessation medications (such as varenicline and bupropion) and of other nAChR ligands.The combination of the IVSA paradigm with pharmacological and genetic tools (e.g., knockout animals) has greatly contributed to our understanding of the role of specific subtype nAChRs in nicotine reinforcement processes. We also discuss some of the limitations of the IVSA paradigm so these can be taken into consideration when interpreting and designing new studies.