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S059-1

Neuropharmacology of Nicotine Seeking and/or Relapse

Michio Itasaka

Department of Psychophysiology, National Center of Neurology and Psychiatry, Japan

Background/Objective: Nicotine dependence and its neural mechanisms have been well
documented by pharmacological, behavioral and neuroscience studies. In this review, we introduce
recent new findings in this theme, particularly focusing on the role of nicotine-associated stimuli as
non-pharmacological factors affecting maintaining/reinstating nicotine seeking.

Method: By using the techniques of drug self-administration and conditioned place preference,
nicotine’s specific property of forming seeking/taking behavior is well characterized, and the
mechanisms of seeking/taking could be partly explained by discrete and/or contextual conditioned
stimuli (dCS and cCS).

Result: After having the repeated Pavlovian conditioning in the training/conditioning sessions, CSs
begin to play a key role for eliciting nicotine seeking behavior, with the activation of mesolimbic
dopaminergic systems. In our study, intracranial self-stimulation (ICSS) was used to assess the
mesolimbic dopamine activity. The nicotine-associated cCS also activated this neural system, which
resulted in decreasing the ICSS threshold approximately 20% in the testing session under the cCS
presentation.

Conclusion: This finding would support the evidence of CS-induced incentive motivation for
nicotine. According to the incentive salience hypothesis, the mesolimbic dopamine reflects the
motivation elicited by incentives (CSs), and induces the drug seeking behavior, which is activated
through amygdala-nucleus accumbens-medial prefrontal cortex circuit. Additionally, human brain
imaging studies have revealed that tobacco-associated stimuli activate not only these regions, but
also right temporo-parietal junction of human cortex, which is relevant to the visual attention. In
summary, the above evidence shows that nicotine-conditioned stimuli may have powerful incentive
salience and regulate nicotine seeking/taking behavior in animals and humans, though stress and
nicotine-withdrawal can also enhance nicotine taking in the similar mechanisms.