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

Abstract

RationaleDecision-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.ObjectiveTo investigate the role of dopamine and serotonin in the interaction between action and valence during learning.MethodsWe combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively.ResultsWe 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.ConclusionsOur findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-013-3313-4) contains supplementary material, which is available to authorized users.

A specific role for serotonin in overcoming effort cost

“…A general role for serotonin in cost processing also seems compatible with the effects on apathy and impulsivity reported in healthy and pathological conditions (Cools et al, 2005; Papakostas et al, 2006; Schweighofer et al, 2008; Crockett et al, 2009; Weber et al, 2009; Warden et al, 2012; Guitart-Masip et al, 2014; Miyazaki et al, 2014; Worbe et al, 2014). Indeed, according to our interpretation, SSRIs might reduce the perceived cost of performing actions, which would promote behavioral activation, hence the alleviation of apathy.…”

“…Indeed, published between-subject comparisons of placebo and anti-depressant treatments were made on a lower sample size per group (e.g. N=14 in Harmer et al, 2004, N=20 in Chamberlain et al, 2006 and N=30 in Guitart-Masip et al, 2014), and a single visit per subject (while we have three). Due to technical problems or late withdrawals, 4 task completions were not fully acquired and therefore unusable.…”

“…Previous studies suggested that serotonin is implicated in the motor aspects of action production and also the valuation processes that motivate the action. Notably, serotonin was found to condition impulse control and the capacity for behavioral inhibition (Cools et al, 2005; Crockett et al, 2009; Warden et al, 2012; Guitart-Masip et al, 2014) and to promote patience for delayed rewards (Schweighofer et al, 2008; Miyazaki et al, 2014; Worbe et al, 2014). Serotonin also impacts the determinants of actions, for instance, how positive and negative outcomes guide learning in humans (Chamberlain et al, 2006; Crockett et al, 2009; Faulkner and Deakin, 2014), monkeys (Clarke et al, 2004) and rodents (Bari et al, 2010).…”

Modeling Trait Anxiety: From Computational Processes to Personality

“…The relative influence of inhibited reward-seeking and potentiated avoidance could depend in part upon interactions between serotonergic and dopaminergic neuromodulation because these neurotransmitters regulate action selection in different ways. For example, inhibition may be mediated by serotonin (194, 195) and response vigor by dopamine [(196); for a review, see Ref. (197)].…”

The role of learning-related dopamine signals in addiction vulnerability

“…Indeed, interference with DA by pharmacological means or by VTA inactivation abolish the ability of Pavlovian CSs to motivate approach and produce PIT (Wassum et al, 2011;Murschall and Hauber, 2006;Lex and Hauber, 2008), and DA stimulation promotes it (Wyvell and Berridge, 2000); whereas model-based behaviour is often rather more resilient to DA manipulations (e.g. Wassum et al 2011; though see Wunderlich et al 2012b;Guitart-Masip et al 2013). Thus, the admittedly very speculative suggestion is that tonic levels of dopamine in the NAcc core differentially modulate the expression of model-free values, and thereby differentially affect sign-trackers.…”