Comparable roles for serotonin in rats and humans for computations underlying flexible decision-making
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Comparable roles for serotonin in rats and humans for computations underlying flexible decision-making. / Luo, Qiang; Kanen, Jonathan W.; Bari, Andrea; Skandali, Nikolina; Langley, Christelle; Knudsen, Gitte Moos; Alsiö, Johan; Phillips, Benjamin U.; Sahakian, Barbara J.; Cardinal, Rudolf N.; Robbins, Trevor W.
In: Neuropsychopharmacology, Vol. 49, No. 3, 2024, p. 600-608.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Comparable roles for serotonin in rats and humans for computations underlying flexible decision-making
AU - Luo, Qiang
AU - Kanen, Jonathan W.
AU - Bari, Andrea
AU - Skandali, Nikolina
AU - Langley, Christelle
AU - Knudsen, Gitte Moos
AU - Alsiö, Johan
AU - Phillips, Benjamin U.
AU - Sahakian, Barbara J.
AU - Cardinal, Rudolf N.
AU - Robbins, Trevor W.
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2024
Y1 - 2024
N2 - Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive–compulsive disorder. However, a unifying mechanistic framework accounting for the role of serotonin in behavioral flexibility has remained elusive. Here, we demonstrate common effects of manipulating serotonin function across two species (rats and humans) on latent processes supporting choice behavior during probabilistic reversal learning, using computational modelling. The findings support a role of serotonin in behavioral flexibility and plasticity, indicated, respectively, by increases or decreases in choice repetition (‘stickiness’) or reinforcement learning rates following manipulations intended to increase or decrease serotonin function. More specifically, the rate at which expected value increased following reward and decreased following punishment (reward and punishment ‘learning rates’) was greatest after sub-chronic administration of the selective serotonin reuptake inhibitor (SSRI) citalopram (5 mg/kg for 7 days followed by 10 mg/kg twice a day for 5 days) in rats. Conversely, humans given a single dose of an SSRI (20 mg escitalopram), which can decrease post-synaptic serotonin signalling, and rats that received the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which destroys forebrain serotonergic neurons, exhibited decreased reward learning rates. A basic perseverative tendency (‘stickiness’), or choice repetition irrespective of the outcome produced, was likewise increased in rats after the 12-day SSRI regimen and decreased after single dose SSRI in humans and 5,7-DHT in rats. These common effects of serotonergic manipulations on rats and humans—identified via computational modelling—suggest an evolutionarily conserved role for serotonin in plasticity and behavioral flexibility and have clinical relevance transdiagnostically for neuropsychiatric disorders.
AB - Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive–compulsive disorder. However, a unifying mechanistic framework accounting for the role of serotonin in behavioral flexibility has remained elusive. Here, we demonstrate common effects of manipulating serotonin function across two species (rats and humans) on latent processes supporting choice behavior during probabilistic reversal learning, using computational modelling. The findings support a role of serotonin in behavioral flexibility and plasticity, indicated, respectively, by increases or decreases in choice repetition (‘stickiness’) or reinforcement learning rates following manipulations intended to increase or decrease serotonin function. More specifically, the rate at which expected value increased following reward and decreased following punishment (reward and punishment ‘learning rates’) was greatest after sub-chronic administration of the selective serotonin reuptake inhibitor (SSRI) citalopram (5 mg/kg for 7 days followed by 10 mg/kg twice a day for 5 days) in rats. Conversely, humans given a single dose of an SSRI (20 mg escitalopram), which can decrease post-synaptic serotonin signalling, and rats that received the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which destroys forebrain serotonergic neurons, exhibited decreased reward learning rates. A basic perseverative tendency (‘stickiness’), or choice repetition irrespective of the outcome produced, was likewise increased in rats after the 12-day SSRI regimen and decreased after single dose SSRI in humans and 5,7-DHT in rats. These common effects of serotonergic manipulations on rats and humans—identified via computational modelling—suggest an evolutionarily conserved role for serotonin in plasticity and behavioral flexibility and have clinical relevance transdiagnostically for neuropsychiatric disorders.
U2 - 10.1038/s41386-023-01762-6
DO - 10.1038/s41386-023-01762-6
M3 - Journal article
C2 - 37914893
AN - SCOPUS:85175379955
VL - 49
SP - 600
EP - 608
JO - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
SN - 0893-133X
IS - 3
ER -
ID: 380213527