Indeed, such a compound might prevent the occurrence of the withdrawal phase and dysregulation of the reinforcement mechanism that is known to be involved in compulsive smoking.
Tobacco smoke contians several substances. Of them, nicotine appears to be the critical reinforcing component of tobacco smoke. A large body of evidence implicates a4b2 nAChrs in the reinforcing effects of nicotine. The initial effect of nicotine is probably to activate 42-nicotinic acetylcholine receptors located on dopamine neurons in the ventral tegmental area; however, it is likely that these receptors are rapidly desensitized, whereas nicotine produces a sustained effect on dopamine release in the nucleus accumbens (Foll and George, 2007). Bupropion and varenicline are accepted as therapy for niocotine addiction. Bupropion can block nicotinic receptor function. varenicline however is a partial agonist or an antagonist depending on the state of activation of the a4b2 receptors. Through its intrinsic partial activation of the 42-nicotinic acetylcholine receptors, varenicline may elicit a moderate and sustained increase in mesolimbic dopamine levels, which would counteract the low dopamine levels encountered in the absence of nicotine during smoking cessation attempts.