Cue dependency of nicotine
self-administration and smoking

Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S,
Gharib MA, Hoffman A, Perkins KA, Sved AF.
Department of Psychology,
455 Langley Hall, University of Pittsburgh,
Pittsburgh, PA 15260, USA.
Pharmacol Biochem Behav 2001 Dec;70(4):515-30


A paradox exists regarding the reinforcing properties of nicotine. The abuse liability associated with smoking equals or exceeds that of other addictive drugs, yet the euphoric, reinforcing and other psychological effects of nicotine, compared to these other drugs, are more subtle, are manifest under more restricted conditions, and do not readily predict the difficulty most smokers experience in achieving abstinence. One possible resolution to this apparent inconsistency is that environmental cues associated with drug delivery become conditioned reinforcers and take on powerful incentive properties that are critically important for sustaining smoking in humans and nicotine self-administration in animals. We tested this hypothesis by using a widely employed self-administration paradigm in which rats press a lever at high rates for 1 h/day to obtain intravenous infusions of nicotine that are paired with two types of visual stimuli: a chamber light that when turned on signals drug availability and a 1-s cue light that signals drug delivery. We show that these visual cues are at least as important as nicotine in sustaining a high rate of responding once self-administration has been established, in the degree to which withdrawing nicotine extinguishes the behavior, and in the reinstatement of lever pressing after extinction. Additional studies demonstrated that the importance of these cues was manifest under both fixed ratio and progressive ratio (PR) schedules of reinforcement. The possibility that nicotine-paired cues are as important as nicotine in smoking behavior should refocus our attention on the psychology and neurobiology of conditioned reinforcers in order to stimulate the development of more effective treatment programs for smoking cessation.
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Nicotine : structure
Parkinson's disease
Smoking and MAO-A
Smoking and MAO-B
Nicotine neuroprotection
Nicotine: an antidepressant?
Nicotine, dopamine and reward
Muscarinic + nicotinic receptors
Nicotine and the cannabinoid system
Nicotine and the dopamine d3 receptors
Nicotine, pleasure, and reward sensitization
Quitting smoking: the role of antidepressants

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