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  • Print publication year: 2020
  • Online publication date: July 2020

3 - Sensitization of Incentive Salience and the Transition to Addiction

from Part I - Concepts of Addiction


Addiction is characterized by excessive desire for a particular substance or behavioral incentive at the expense of other life rewards. Addictive desire can develop even in absence of any associated increase in pleasure, and also in absence of withdrawal. Here we review evidence that the brain mechanisms underlying desire or ‘wanting’ can operate independently from those mediating pleasure, or "liking." That is, "wanting" and "liking" are mediated by two anatomically and neurochemically distinct brain mechanisms that normally interact together to influence motivation, but can become dissociated in the transition to addiction. Pleasure "liking" is the hedonic impact of a pleasant stimulus and is causally amplified by a brain system of several functionally interactive but anatomically distributed locations referred to as "hedonic hotspots." These hedonic hotspots are localized subregions within larger brain structures, and are relatively sensitive to disruption. By contrast, "wanting" or the subconscious desire for reward or reward-related cues is much more robust, and mediated by a larger brain system. "Wanting" can be generated by dopamine enhancements as well as by opioid enhancements in several broadly defined regions throughout mesocorticolimbic circuitry. In susceptible individuals, mesolimbic circuitry can become hyperreactive or sensitized (e.g., through previous drug experience), so that "rewards" and their related cues evoke even greater dopamine release and "wanting." Sensitized "wanting" becomes harder to resist, which can spur on excessive and compulsive pursuit and relapse in addiction. Importantly, this sensitization of brain "wanting" systems need not be accompanied by an enhancement of brain "liking" (i.e., dopamine manipulations do not appear to effect pleasure). In this chapter, we also highlight possible mechanisms for how some drugs or behaviors become the specific focus of excessive but narrow pursuit, usually involving mesolimbic brain interactions with areas such as the amygdala. Further we demonstrate that behavioral addictions such as food addiction and gambling, like drug addiction, are accompanied by sensitization of mesolimbic brain "wanting" systems in the transition to addiction.

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