A selective role for dopamine in stimulus-reward learning

Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control.     

Molecular identification of a renal urate anion exchanger that regulates blood urate levels

Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences. Here we identify the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution.