'A selective role for dopamine in stimulus-reward learning'
Nature 469:53-57.
By Flagel SB, Clark JJ, Robinson TE, Mayo L, Czuj A, Willuhn I, et al.
What is it?
In support of this theory, there is considerable evidence to suggest that drug-associated stimuli become more salient or noticeable to drug abusers. Substance abusers show attentional biases or preferentially attend to drug-related pictures (Bradley et al., 2004; Field et al., 2006) and words (see Cox et al., 2006 for review). They also demonstrate positive biases in the evaluation of drug-related cues and in their tendency to approach such cues (Bradley et al., 2004; Mogg et al., 2003; Field et al., 2004, 2005).
Overview of experimental studies
Individual differences in the CR
Differences between sign-trackers and goal-trackers
‘individual differences in the tendency to attribute incentive salience to reward-predictive cues may confer vulnerability or resistance to compulsive behavioural disorders, including addiction. Thus, we suggest that the distinction between the sign-tracking and goal-tracking phenotype may provide a means with which to explore individual differences in the tendency to attribute incentive value to reward-predictive cues, and their ability to gain inordinate control over behaviour’.
Relationship with response to novelty
After characterization of the HR/LR phenotype, this group then tested whether HR or LR rats could develop a CR to non-contingent intravenous cocaine administration [non-contingent means that the animals don't have to do anything to receive a cocaine infusion; it is independent of their behaviour]. As expected, HR rats had a much greater tendency to approach the lever signalling cocaine administration than LR rats. Interestingly, HR rats show a greater sensitivity to the psychomotor effects of the dopaminergic D2/3 receptor agonist [an agonist enhances the biological activity of a system], quinpirole, compared to LR rats, and there are also differences in dopamine D2 receptor binding in the NAcc and dorsal striatum, as well as alterations in phasic dopaminergic events in the NAcc core. HR have lower dopamine D2 mRNA levels but a much greater proportion of high affinity receptors; they also show an increased number of spontaneous dopaminergic events but do not differ from LR in terms of food-induced dopamine release: sorry if this is all a little bit tedious; basically, it's sufficient to know that there are a number of neurobiological differences between HR and LR within the dopamine system!
The CR, dopamine, and LEARNING...
It is thought that once learning has occurred and the reward is no longer surprising, there is no longer a dopamine signal when the reward is received, and instead, the signal passes to the event of the cue, which IS unexpected.
The function of these phasic changes in dopamine has been a source of great debate amongst researchers, and there are two main theories:
- Dopamine updates the predictive value of the cues during associative learning or makes the process more efficient.
- Changes in dopamine are responsible for the attribution of incentive salience to cues as they become rewarding in their own right.
Flagel et al. (2011) used the sign-tracking model to separate these two components as it exploits the differences between animals regarding their tendency to attribute incentive value to cues. As the CS acts as an equivalent predictor of reward for both sign- and goal-trackers, producing CRs that emerge at the same time, if the phasic changes in dopamine mediate the predictive value of cues, then they should be apparent in all rats. However, if dopamine is, in fact, mediating the incentive value of cues, then only sign-tracker rats should show changes in dopamine as they attribute incentive value to the CS...
Fast-scan cyclic voltammetry was used to characterize changes in dopamine signalling in the NAcc core during Pavlovian conditioning in HR (sign-tracking) and LR (goal-tracking) rats. It was found that sign-trackers showed a decreased dopamine response to the reward and an increased response to the CS, while goal-trackers maintained almost identical responses to both the reward and the CS. These data show that changes in dopamine signalling only occur in sign-tracking rats, or rats that attribute incentive salience to cues, and not in rats that are goal-directed, suggesting that different neuronal circuits mediate different CRs resulting from stimulus-reward associations. This is beautiful stuff!
Such a ground-breaking study illustrates the utility of behavioural phenotyping and how it can be applied to any type of research question: it should always be kept in mind that quantifiable behavioural output from animals is simply an observable manifestation of underlying differences in brain function, which can mediate multiple disparate or interacting processes. We are only just beginning to realise the potential that such exploitation of inter-individual differences holds, with this study representing a major advance in the field, and opening up many new avenues of research.