Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.
Authors
Apergis-Schoute, Annemieke M
Yellowlees, Robyn
Arntz, Fréderique E
van der Flier, Febe E
Price, Annabel
Crockett, Molly J
Publication Date
2021-12Journal Title
Mol Psychiatry
ISSN
1359-4184
Publisher
Springer Science and Business Media LLC
Volume
26
Issue
12
Pages
7200-7210
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Kanen, J. W., Apergis-Schoute, A. M., Yellowlees, R., Arntz, F. E., van der Flier, F. E., Price, A., Cardinal, R. N., et al. (2021). Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.. Mol Psychiatry, 26 (12), 7200-7210. https://doi.org/10.1038/s41380-021-01240-9
Description
Funder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370
Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272
Abstract
Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.
Keywords
Article, /631/477, /631/378, article
Sponsorship
NIHR
Funder references
Medical Research Council (MC_PC_17213)
Wellcome Trust (104631/Z/14/Z)
Identifiers
s41380-021-01240-9, 1240
External DOI: https://doi.org/10.1038/s41380-021-01240-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334415
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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