Reinforcement enhancement by nicotine in adult rats: behavioral selectivity and relation to mode of delivery and blood nicotine levels

Reinforcement-enhancing effects of nicotine occur in human subjects and laboratory rats. However, the doses used in animal studies typically exceed smoking-associated levels of exposure, and generalized behavioral activation by nicotine can potentially confound data interpretation. During daily 60-min sessions, male adult rats pressed an active lever to illuminate a brief cue light. Pressing on either the active or inactive lever retracted both levers for 60 s. Nicotine (0.025-0.2 mg/kg) was given either by continuous intravenous (IV) infusion, or spaced IV pulses (3-s or 30-s/pulse), or pre-session subcutaneous (SC) injection. Almost all rats responded preferentially for the cue light for several weeks. After several home-cage nicotine injections, reinforcement enhancement occurred even within the first nicotine test session. Nicotine increased active lever responding without altering inactive lever responding, with effects reliably observed at doses as low as 0.1 mg/kg SC or 0.1 mg/kg/session IV. Within the session, the 0.1 mg/kg dose maximally increased active lever responding by 2-3-fold, coinciding with serum levels of 25 ng/ml. Intravenous nicotine (tested at 0.1 mg/kg/60-min session) was equally effective whether delivered by continuous infusion or in a series of equally spaced 0.003 mg/kg pulses each of 3-s or 30-s duration. Low doses of nicotine can potentiate responding for a primary sensory reinforcer without producing a generalized increase in lever pressing. Reinforcer enhancement by nicotine generalized to several modes of drug delivery, appeared to track circulating levels of drug, and occurred even at serum levels within the daytime range of moderate cigarette smokers.