ReviewImaging dopamine's role in drug abuse and addiction
Introduction
Drugs of abuse trigger large increases in extracellular dopamine (DA) in limbic regions (including nucleus accumbens; NAc) (Di Chiara and Imperato, 1988, Koob and Bloom, 1988), which are associated with their reinforcing effects. These effects mimic but surpass the DA increases secondary to phasic DA cell firing that play a physiological role in coding for saliency and reward (Schultz et al., 2000). Though some animal studies have questioned the extent to which DA increases in NAc are associated with reward (Drevets et al., 2001, Day et al., 2007), human imaging studies have shown that drug-induced increases in DA in the striatum (including the ventral striatum, where the NAc is located) are associated with subjective descriptors of reward (high, euphoria) (Volkow et al., 1996a, Drevets et al., 2001). Nevertheless, it is also evident that the firing rate of DA cells encode not just reward (Tobler et al., 2007) and expectancy of reward (Volkow et al., 2003b) but also the saliency of a given event or stimulus (Rolls et al., 1984, Williams et al., 1993, Horvitz, 2000, Zink et al., 2003). The saliency of an event is driven either by its unexpectedness, its novelty, its conditioned expectations or its reinforcing effects (positive as well as negative) (Volkow et al., 2003a, Volkow et al., 2006b). Firing of DA cells, concomitant to the use of the drug will also facilitate the consolidation of memory traces connected to the drug. These, in turn, will trigger DA cells firing with future exposure to stimuli associated with the drug (in expectation of the reward) (Waelti et al., 2001). Because of DA's role in motivation, the DA increases associated with drug-cues or the drug itself are also likely to modulate the motivation to procure the reward (McClure et al., 2003).
The increase in knowledge regarding the multiple roles of DA in the reinforcement processes has led to more complex models of drug addiction. It is currently believed that drugs are reinforcing not just because they are pleasurable but because, by increasing DA, they are being processed as salient stimuli that will inherently motivate the procurement of more drug (regardless of whether the drug is consciously perceived as pleasurable or not).
Brain imaging techniques have contributed greatly to this new understanding. They have allowed us to measure neurochemical and metabolic processes in the living human brain (Volkow et al., 1997a), to investigate the nature of the changes in DA induced by drugs of abuse and their behavioral relevance, and to study the plastic changes in brain DA activity and its functional consequences in drug addicted subjects. This paper provides an updated review of relevant findings.
Section snippets
Drug-induced dopamine increases in the human brain and in reinforcement
The use of positron emission tomography (PET) and specific D2 DA receptor radioligands (e.g., [11C]raclopride, [18F]N-methylspiroperidol) has proven invaluable for the study of the relationships between a drug's ability to modulate DA and its reinforcing (i.e., euphorigenic, high-inducing, drug-liking) effects in the human brain. The approach has been used effectively to assess the effects of stimulant drugs (i.e., methylphenidate, amphetamine, cocaine) as well as those of nicotine (Barrett
Role of dopamine in the long-term effects of drugs of abuse on DA in the human brain: involvement in addiction
Synaptic increases in DA occur during drug intoxication in both addicted as well as non-addicted subjects (Di Chiara and Imperato, 1988, Koob and Bloom, 1988). However, only a minority of exposed subjects—the actual proportion being a function of the type of drug used—ever develops a compulsive drive to continue taking the drug (Schuh et al., 1996). This indicates that the acute drug-induced DA increase alone cannot explain the ensuing development of addiction. Because drug addiction requires
DA and vulnerability to drug abuse
Understanding why some individuals are more vulnerable to becoming addicted to drugs than others remains one of the most challenging questions in drug abuse research. In healthy non-drug abusing controls we showed that D2 DA receptor availability in the striatum modulated their subjective responses to the stimulant drug methylphenidate. Subjects describing the experience as pleasant had significantly lower levels of receptors compared with those describing methylphenidate as unpleasant (Volkow
Treatment implications
Imaging studies have corroborated the role of DA in the reinforcing effects of drugs of abuse in humans and have extended traditional views of DA involvement in drug addiction. These findings suggest multiprong strategies for the treatment of drug addiction that should attempt to (a) decrease the reward value of the drug of choice and increase the reward value of non-drug reinforcers; (b) weaken conditioned drug behaviors, and the motivational drive to take the drug; and (c) strengthen frontal
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