Differential, but not opponent, effects of l-DOPA and citalopram on action learning with reward and punishment

RATIONALE: Decision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing. OBJECTIVE: To investigate the role of dopamine and serotonin in the interaction between action and valence during learning. METHODS: We combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively. RESULTS: We found that, after administration of levodopa, action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control. Citalopram had distinct effects, increasing participants’ tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition. CONCLUSIONS: Our findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00213-013-3313-4) contains supplementary material, which is available to authorized users.