The Role of Nicotine Reward

The authors are aware that if a drug sustains drug-taking behavior, that is, nicotine self-administration or smoking, this does not tell how it does so. Many factors have been proposed to contribute to the overall positive reinforcing efficacy of the drug, that is, nicotine reward, and these have been reviewed extensively (8,10,12,22). Accordingly, a drug may:

1. Reinforce the stimulus-response habit directly

2. Modulate internal affective states and producing euphoria or reducing anxiety

3. Modulate other reinforcer effects for example, enhancing social or sexual reinforcers

4. Modulate attentional or perceptual mechanisms

It has been suggested that the first and second are distinctive mechanisms by which the drug acts directly on the neural substrate and mediate the reinforcing properties, whereas for the third and fourth the drug exerts its effects indirectly (12).

In drug self-administration the subject starts by learning about the response-outcome contingency (incentive, stimulus-reward learning, goal-oriented behavior), and then the action gradually becomes a habit (stimulus-response learning). Certain addictive drugs may influence self-administration behavior by acting on stimulus-reward learning, leading to the acquisition of a drug-reinforced habit over time (23,24). In this case environmental stimuli can become associated with the effects of the drugs, acquiring secondary reinforcing properties (conditioned reinforcer). Interestingly, using so called second-order schedules, conditioned reinforcers may take control over operant responding, indicating persistence of drug-taking induced by conditioned cues in the absence of the drug. It has been argued that, at least for human studies, substance use (i.e., smoking) is habitual, and relapse is most often triggered by exposure to eliciting cues, including environmental conditioned stimuli described above, or a priming stimulus with a single dose of the same drug (8,25). In the latter case, the drug acts as a discriminative stimulus, producing interoceptive effects that contribute to the initiation of drug-taking behavior. Interestingly, low doses of nicotine can induce relapse of nicotine self-administration in rats following extinction (26,27). White (22) maintains that both forms of stimulus-reward and stimulus-response leaning coexist in parallel in the brain of subjects who self-administer addictive drugs, and this appears particularly true for nicotine (10). Eliciting cues, both environmental and interoceptive-discriminant, play an important role in determining the subjective feeling of craving for the drug. These conditioned processes have to be taken into account when addressing experiments on the molecular correlates of self-administration procedures. However, it is believed that they play important roles in sustaining drug self-administration only if the drug is able to maintain its activating properties on the neural substrate of the reward system over time.

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