The Role of Mesoaccumbens Dopamine in Nicotine Dependence

Abstract

There is abundant evidence that the dopamine (DA) neurons that project to the nucleus accumbens play a central role in neurobiological mechanisms underpinning drug dependence. This chapter considers the ways in which these projections facilitate the addiction to nicotine and tobacco. It focuses on the complimentary roles of the two principal subdivisions of the nucleus accumbens, the accumbal core and shell, in the acquisition and maintenance of nicotine-seeking behavior. The ways in which tonic and phasic firing of the neurons contributes to the ways in which the accumbens mediate the behavioral responses to nicotine are also considered. Experimental studies suggest that nicotine has relatively weak addictive properties which are insufficient to explain the powerful addictive properties of tobacco smoke. This chapter discusses hypotheses that seek to explain this conundrum. They implicate both discrete sensory stimuli closely paired with the delivery of tobacco smoke and contextual stimuli habitually associated with the delivery of the drug. The mechanisms by which each type of stimulus influence tobacco dependence are hypothesized to depend upon the increased DA release and overflow, respectively, in the two subdivisions of the accumbens. It is suggested that a majority of pharmacotherapies for tobacco dependence are not more successful because they fail to address this important aspect of the dependence.

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

“…There is abundant evidence that the reinforcing properties of nicotine depend upon stimulation of DA neurones in the ventral tegmental area that project to the nucleus accumbens (see Balfour 2015 for review). The ability of psychostimulant drugs, such as nicotine, to serve as reinforcers in selfadministration experiments have been particularly related to increased DA release in the shell subdivision of the accumbens.…”

“…Thus, it seems likely that, while the addiction to tobacco smoke requires the presence of nicotine, other components of tobacco smoke also contribute significantly to the addiction (Balfour 2015). Although there are a number of chemical components within tobacco smoke that may enhance the addictive properties of nicotine, much attention has been focused on the role of sensory stimuli within the smoke in the development of dependence.…”

“…Repetitive non-contingent daily injections of nicotine result in sensitisation of the locomotor stimulation evoked by the drug. However, there is evidence that two mechanisms may underpin this phenomenon -a pharmacological sensitisation that is independent of context and a contextually-conditioned sensitisation that depends upon repeated association between the drug and the context in which it is delivered (Balfour 2015).…”

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 These results, when taken together, imply that MPEP attenuates the expression of behavioural responses to nicotine that are conditioned to the context in which nicotine is administered. Balfour (2015) speculated that the increase in extracellular DA, evoked in the nucleus accumbens by nicotine, may play an important role in establishing the motivational salience of conditioned context cues.…”

“…Novel treatments, therefore, need to be able to accommodate these "difficult to treat" smoker populations. While it is clear that nicotine is the principal addictive component of tobacco smoke, studies in humans and with animal models suggest that its addictive properties are not sufficiently potent to explain the powerful addiction to tobacco smoke experienced by a majority of habitual smokers (Caggiula et al 2001;Balfour 2015).…”