The brain’s subcortical dopamine circuitry promotes approach and engagement (“go”) but is often opposed by the inhibitory control (“stop”) exerted by the prefrontal cerebral cortex. Addictive drugs effectively engage the “go” system, and the inhibitory control is often deficient in addicted individuals, a result of either heavy drug use or a pre-existing condition. Repeated activation of the “go” circuits causes neuroadaptation that lessens the euphoric drug effects, resulting in withdrawal syndrome and lingering dysphoria when drug use stops. Persistent and compulsive drug-seeking then emerges as reinforcement shifts from predominantly positive and pleasurable, to the negative reinforcement of relief from dysphoria. Drug-seeking behavior is also strengthened as dopamine activation results in conditioning of stimuli predicting drug effects. Increased glutamate activity promotes development of incentive sensitization, thought to underlie the strong response to drug-related stimuli that drive the compulsion for drug use even after the initial rewarding effect is greatly reduced – producing the “wanting, but not liking” dissociation often seen in 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.