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Abstract:Rationale: The importance of reward-associated cues in eliciting behavior is well established, with stimuli associated with drugs of abuse known to play a crucial role in recidivism. Recently, Redish (2004) proposed that drugs, acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS), meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism to explain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependence problems in general.Objectives: We tested whether pairings between nicotine and an environmental CS would convey conditioned reinforcement properties onto the CS, even when nicotine's rewarding effects were already fully predicted by another cue (whether there was an absence of the blocking effect).Methods: 134 male Long-Evans rats were implanted with jugular catheters and assigned to either food-or nicotine-reward (0.06 mg/kg/inf) conditions. Each group was exposed to paired or unpaired presentations of their respective reward with one CS in 10 daily sessions; subsequently, they were exposed to 4 more daily sessions of paired presentations of the reward paired with a compound CS composed of the original CS and a second CS. Tests of the conditioned reinforcing value of both CSs using the active-lever-presses to total-presses ratio as an outcome were conducted following training.Results: Pressing for a blocked second CS (µ = 0.59, SD = 0.21) was significantly lower than pressing for an unblocked second CS (µ = 0.69, SD = 0.14) in the food-reward condition, but not in nicotine-rewarded animals, verifying the hypothesis that nicotine, but not food, is resilient to the blocking effect. Conclusion:The absence of blocking when nicotine is the reward may explain the powerful role for cues in supporting tobacco dependenceby allowing for the extension of nicotine's rewarding value across numerous associated cues.