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Using environmental cues to predict rewarding events is essential for adaptive behaviour in humans and animals alike. Dopamine is strongly implicated in this process of reinforcement learning, specifically phasic changes in dopamine release in the ventral striatum, which correlate with a reward prediction error signal necessary for such learning. However, while much is known about striatal dopamine, it is unclear what influence dopamine in other brain regions, particularly the cortex, might play in mediating other factors that influence how such associations are acquired and expressed. To address this issue, we have investigated the behaviour and neurochemistry of a transgenic mouse model which exhibits lower levels of dopamine turnover in the cortex by mimicking a polymorphism found in the human catechol-O-methyltransferase gene (COMT Val158Met). I will present a series of experiments that reveals that COMT genotype affects reinforcement learning in a manner that is dependent on cue salience. I will then relate this effect to specific and selective changes in phasic dopamine release in the ventral striatum. Taken together, these experiments show that COMT genotype – and by implication, cortical dopamine – impacts striatal dopamine release during learning and controls the selection of a particular behavioural response to a reward-associated, salient cue.
