Self-administration of 5-iodo-A-85380, a beta2-selective nicotinic receptor ligand, by operantly trained rats

It is widely accepted that nicotine is the active ingredient of tobacco smoke that promotes tobacco dependence. Nicotine interacts with several subtypes of nicotinic acetylcholine receptors (nAChRs). In brain, it primarily targets nAChRs that contain beta2 and alpha4 subunits in combination and those composed of solely alpha7 subunits. The present study tested whether operantly trained rats would self-administer a ligand active at beta2-containing (i.e. not alpha7) nAChRs. Male Sprague-Dawley rats were trained to lever press for i.v. cocaine self-administration. After 2 weeks of cocaine washout, rats were given operant access to 5-iodo-A-85380 (5IA), a beta2-selective nAChR ligand, in daily 1 h sessions. The rats rapidly developed a stable level of 5IA self-administration behavior (unit dose = 5 nmol/kg/infusion). This finding suggests that interaction with beta2-containing nAChRs, without direct involvement of alpha7 receptors, can produce reinforcement and thereby can support self-administration behavior.