A second-order schedule of food reinforcement in rats to examine the role of CB1 receptors in the reinforcement-enhancing effects of nicotine.

Nicotine is believed to enhance the motivational value of reinforcers. Although endogenous cannabinoids acting on CB1 receptors have been implicated in the motivational effects of nicotine, their role in the 'reinforcement-enhancing' properties of nicotine is unknown. This study compared the effect of acute and chronic non-contingent nicotine administration on responding for an unconditioned reinforcing stimulus (UCS) and a visual conditioned stimulus (CS) and the role of CB1 receptors was examined. Male hooded Lister rats were trained on a second-order schedule [FI 15' (FR5: S)] under which presentation of the CS (5s/5Hz light oscillation) was intermittently reinforced by the UCS (food). The rats were treated with daily saline or nicotine (0.4 mg/kg, subcutaneous [s.c.]) throughout the study. The effect of the acute nicotine challenge (0.05, 0.1 and 0.2 mg/kg, s.c.) and the CB1 receptor antagonist AM251 (0.1, 0.3 and 1 mg/kg, intraperitoneal [i.p.]) on responding for the CS and/or UCS was examined. The acute nicotine challenge increased responding for both the UCS and CS in the rats chronically treated with nicotine, an effect which was less robust in the nicotine-naive rats. AM251 significantly reduced responding for the UCS and CS, and an interaction with the nicotine challenge was found. These data support and extend the hypothesis that nicotine can enhance the motivational value of reinforcing stimuli and suggest the increases in responding produced by nicotine involve CB1 receptors. Furthermore, this study highlights the utility of second-order schedules of reinforcement for investigation of the neural circuits underlying the reinforcement-enhancing effects of nicotine.