title: Cortisol administration induces global down-regulation of the brain's reward circuitry.
abstract: Research in rodents and humans has shown divergent effects of the glucocorticoids corticosterone and cortisol (CRT) on reward processing. In rodents, administration of CRT increases reward drive by facilitating dopamine release in the ventral striatum. In humans, correspondingly, risky decision-making increases when CRT levels are elevated. Human stress studies contrariwise show that elevated CRT is accompanied by a decrease in reward-related brain activity. There are however no direct insights into how CRT acts on the reward system in the human brain. Accordingly, we used pharmacological functional magnetic resonance imaging (pharmaco-fMRI) to investigate the effects of CRT on the brain's reward system. In a randomized within-subject design we administered a high dose of CRT (40 mg) and placebo to twenty healthy male volunteers on separate days, and used a monetary incentive delay task to assess the effects of the hormone on the striatum and the amygdala in anticipation of potential reward. In contrast to animal studies, we show that this high dose of CRT strongly decreases activity of the striatum in both reward and non-reward conditions. Furthermore, we observed reductions in activity in the basolateral amygdala, a key regulator of the brain's reward system. Crucially, the overall down-regulation of the brain's reward circuit was verified on the subjective level as subjects reported significantly reduced reward preference after CRT. In sum, we provide here direct evidence in humans that CRT acts on brain regions involved in reward-related behavior, that is, the basolateral amygdala and the striatum. Our findings suggest that CRT in the quantity and time course presently used globally down-regulates the reward system, and thereby decreases motivational processing in general.
authors.affiliation: Department of Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands. Electronic address: e.r.montoya@uu.nl.
authors.forename: Estrella R
authors.initials: ER
authors.lastname: Montoya
authors.affiliation: Department of Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands; Department of Psychiatry, University of Cape Town, Cape Town 7925, South Africa.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bos
authors.affiliation: Department of Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands; Department of Psychiatry, University of Cape Town, Cape Town 7925, South Africa.
authors.forename: David
authors.initials: D
authors.lastname: Terburg
authors.affiliation: Department of Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rosenberger
authors.affiliation: Department of Experimental Psychology, Utrecht University, 3584 CS Utrecht, The Netherlands; Department of Psychiatry, University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa.
authors.forename: Jack
authors.initials: J
authors.lastname: van Honk
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009042:Motivation / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D012201:Reward; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D055815:Young Adult
chemical_list: D006854:Hydrocortisone
keywords: Amygdala; Cortisol; Nucleus accumbens; Reward anticipation; Striatum