Dual contributions of noradrenaline to behavioural flexibility and motivation

Abstract

IntroductionWhile several theories have highlighted the importance of the noradrenergic system for behavioral flexibility, a number of recent studies have also shown a role for noradrenaline in motivation, particularly in effort processing. Here, we designed a novel sequential cost/benefit decision task to test the causal influence of noradrenaline on these two functions in rhesus monkeys.MethodsWe manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels and examined how this manipulation influenced performance on the task. ResultsClonidine had two specific and distinct effects: first, it decreased choice variability, without affecting the cost/benefit trade-off; and second, it reduced force production, without modulating the willingness to work.ConclusionsTogether, these results support an overarching role for noradrenaline in facing challenging situations in two complementary ways: by modulating behavioral volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges.Electronic supplementary materialThe online version of this article (10.1007/s00213-018-4963-z) contains supplementary material, which is available to authorized users.

Pharmacological evidence for the implication of noradrenaline in effort

“…Indeed, at that time, the firing of LC neurons scales positively with the costs and negatively with the reward levels, suggesting that LC activation is related to the mobilization of resources necessary for overcoming that difficulty [33,46,47]. In line with an interpretation in terms of physical effort, we recently showed a strong effect of noradrenergic manipulation on the amount of exerted force in a task in which force was not instrumental [48]. What remains unclear, however, is the extent to which noradrenergic manipulations would affect effort, defined as a single computational variable affecting both choices and force production.…”

Noradrenergic But Not Dopaminergic Neurons Signal Task State Changes and Predict Reengagement After a Failure

“…Catecholaminergic neuromodulation is thought to be critical for numerous aspects of behaviour, including motivation, learning, decision-making and behavioural flexibility ( the magnitude of this activation seems to be related to the amount of effort necessary to trigger the action (Bouret & Richmond, 2015;Varazzani et al, 2015). In line with this interpretation, we recently used a pharmacological manipulation to demonstrate directly that, on top of its role in behavioural flexibility, noradrenaline was also causally involved in motivation (Jahn et al, 2018). One interpretation of the dual role of noradrenergic LC neurons in behavioural flexibility and motivation is that flexibility relies upon their response to unexpected stimuli whereas their role in motivation relies upon their activation at the triggering of effortful actions.…”

What Is the Relationship between Dopamine and Effort?

“…For instance, a high response schedule can change the likelihood of initiating an action but not influence simple Pavlovian responses such as appetitive lipping by a monkey in anticipation of the upcoming delivery of water 36 , 87 . Equally, pharmacological manipulations can leave patterns of schedule length-related choice relatively unaltered while modulating the amount of force that is produced [88] . These distinctions are important not only when considering the normative decision-making strategy in different model organisms but also because there is increasing evidence that the neural circuits necessary to assess and overcome different types of effort cost are partially distinct.…”

“…For instance, a high response schedule can change the likelihood of initiating an action but not influence simple Pavlovian responses such as appetitive lipping by a monkey in anticipation of the upcoming delivery of water 36 , 87 . Equally, pharmacological manipulations can leave patterns of schedule length-related choice relatively unaltered while modulating the amount of force that is produced [88] .…”