Enhancement of the conditioned reinforcing properties of stimuli by nicotine in rats.

Rationale: Conditioned environmental stimuli are important determinants of drug-taking and -seeking behaviours. Acute nicotine administration enhances responding with conditioned reinforcement when conditioned stimuli (CS) are previously paired with water reward. However, the effect of acute nicotine on instrumental responding supported by nicotine cues has never been assessed. Objective: The present study investigated the effect of nicotine self-administration and subsequent acute nicotine challenge on responding for conditioned reinforcement by using a procedure in which drug-associated cue supports the acquisition and persistence of responding on a novel lever that had no previous association with the primary reinforcing event. Methods: Male Lister Hooded rats were first trained to self-administer intravenous (i.v.) nicotine (0.03 mg/kg/infusion) by nosepoke paired with a 20-s light conditioned stimulus (CS) with 200 infusions taken in 8 sessions. Animals were then presented with two novel levers and pressing on one (active) lever led to a brief presentation of the CS. Subsequently acute challenges with increasing doses of nicotine (0.0375, 0.075, 0.15, 0.3 mg/kg s.c., Latin-square design) before sessions were made. Additional experiments were performed to confirm the nicotine cue was acting as a conditioned reinforcer. Results: Rats quickly acquired a discriminated responding for the active lever, which persisted and baselined for the duration of the experiments. Acute nicotine (0.15 mg/kg s.c.) significantly increased baseline responding selectively on the active lever, an effect that was significantly blocked by mecamylamine (0.3 and 1 mg/kg, s.c). Switching the lever stimulus contingency led to a reversal of lever pressing confirming the discriminated nature of the stimulus reinforcement. Conclusion: These findings suggest that (1) nicotine-cues act as conditioned reinforcer to support acquisition and persistence of a novel response; 2) the discriminated responding is supported by contingent presentation of the CS and is sensitive to reversal; 3) acute nicotine (in a mecamylamine-reversible manner) increases the conditioned reinforcing properties of nicotine-associated CS in a manner dissociable from concurrent measures of locomotor activity