Concurrent Glucocorticoid and Noradrenergic Activity Shifts Instrumental Behavior from Goal-Directed to Habitual Control

Abstract

Stress modulates instrumental action in favor of habitual stimulus-response processes that are insensitive to changes in outcome value and at the expense of goal-directed action-outcome processes. The neuroendocrine mechanism underlying this phenomenon is unknown. Here, we tested the hypothesis that concurrent glucocorticoid and noradrenergic activity bias instrumental behavior toward habitual performance. To this end, healthy men and women received hydrocortisone, the ␣2-adrenoceptor antagonist yohimbine or both orally before they were trained in two instrumental actions leading to two distinct food outcomes. After training, one of the outcomes was devalued by inviting participants to eat that food to satiety. A subsequent extinction test revealed whether instrumental performance was goal-directed or habitual. Participants that received hydrocortisone or yohimbine alone decreased responding to the devalued action in the extinction test, i.e., they behaved goal-directed. The combined administration of hydrocortisone and yohimbine, however, rendered participants' behavior insensitive to changes in the value of the goal (i.e., habitual). These findings demonstrate that the concerted action of glucocorticoids and noradrenergic activity shifts instrumental behavior from goal-directed to habitual control.

Simultaneous Glucocorticoid and Noradrenergic Activity Disrupts the Neural Basis of Goal-Directed Action in the Human Brain

“…This stress effect can be mimicked by the simultaneous administration of glucocorticoids and an ␣2-adrenoceptor antagonist that increases noradrenergic stimulation (Schwabe et al, 2010b). Glucocorticoids or noradrenergic activation alone, however, did not alter instrumental learning, suggesting that the stress-induced shift toward habit learning requires, similar to stress effects on hippocampusdependent memory (Roozendaal et al, 2006a,b), concurrent glucocorticoid and noradrenergic activity.…”

“…Participants were administered 20 mg of hydrocortisone (Jenapharm) and/or 20 mg of yohimbine (Desma) orally ϳ50 min before learning. Timing and dosage of drug administration were chosen to be in line with our previous study (Schwabe et al, 2010b). To verify the action of the drugs, we took saliva samples at several time points across the experiment.…”

“…If performance is goal-directed, it should be sensitive to the outcome devaluation; the absence of this sensitivity indicates habitual performance. Based on our previous behavioral study (Schwabe et al, 2010b), we expected that only the combined administration of hydrocortisone and yohimbine would induce habit learning. At the neural level, we focused on interactive influences of hydrocortisone and yohimbine on activity in the orbitofrontal cortex, the medial prefrontal cortex, the caudate nucleus, and the putamen because these areas have been implicated in goal-directed and habitual learning in earlier neuroimaging studies (Valentin et al, 2007;Tricomi et al, 2009).…”

Blocking the Mineralocorticoid Receptor in Humans Prevents the Stress-Induced Enhancement of Centromedial Amygdala Connectivity with the Dorsal Striatum

“…Specifically, the MR appears to mediate a shift to more striatal control over behavior, favoring well-learned habit-like responses and stimulus-response learning over controlled, flexible behavior guided by long-term goals (Schwabe et al, 2010b). This might have implications for our understanding of stressrelated mental disorders.…”

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

“…Such phenomena has been shown to mediate stress-dependent cognitive processes; for example, synergy between noradrenergic system and GCs leads to a strong deactivation of PFC areas during emotional encoding in human (van Stegeren et al, 2010), while preclinical research has highlighted the crucial role of GCsnoradrenaline regulatory interactions at multiple levels: (i) at the level of basolateral amygdala for enhancing emotionally arousing-related memory consolidation and social behaviour (Roozendaal et al, 1996;Schwabe et al, 2010) by enhancing synaptic plasticity (Sarabdjitsingh et al, 2012), (ii) at the hippocampal level, where they alter the functional contribution of AMPA receptors to glutamatergic neurotransmission (Zhou et al, 2012), or (iii) at the level of hypothalamus, where they modulate feeding behaviour (Leibowitz et al, 1984; Jhanwar-Uniyal and Roland et al, 1986). Collectively, these combined effects promote behavioural adaptation to stressful situations .…”