The role of the noradrenergic system in the exploration-exploitation trade-off: a pharmacological study
Open accessAbstract
Animal research and computational modeling have indicated an important role for the neuromodulatory locus coeruleus-norepinephrine (LC-NE) system in the control of behavior. According to the adaptive gain theory, the LC-NE system is critical for optimizing behavioral performance by regulating the balance between exploitative and exploratory control states. However, crucial direct empirical tests of this theory in human subjects have been lacking. We used a pharmacological manipulation of the LC-NE system to test predictions of this theory in humans. In a double-blind parallel-groups design (N = 52), participants received 4 mg reboxetine (a selective norepinephrine reuptake inhibitor), 30 mg citalopram (a selective serotonin reuptake inhibitor), or placebo. The adaptive gain theory predicted that the increased tonic NE levels induced by reboxetine would promote task disengagement and exploratory behavior. We assessed the effects of reboxetine on performance in two cognitive tasks designed to examine task (dis)engagement and exploitative versus exploratory behavior: a diminishing-utility task and a gambling task with a non-stationary pay-off structure. In contrast to predictions of the adaptive gain theory, we did not find differences in task (dis)engagement or exploratory behavior between the three experimental groups, despite demonstrable effects of the two drugs on non-specific central and autonomic nervous system parameters. Our findings suggest that the LC-NE system may not be involved in the regulation of the exploration-exploitation trade-off in humans, at least not within the context of a single task. It remains to be examined whether the LC-NE system is involved in random exploration exceeding the current task context.
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Other neurotransmitters (serotonin, oxytocin, norepinephrine) appear to fulfill similar functions in regulating motivation in different motivational domains, such as withdrawal, contentment, affiliation, neural toning down, and curiosity.
“Other neurotransmitters (serotonin, oxytocin, norepinephrine) appear to fulfill similar functions in regulating motivation in different motivational domains, such as those of withdrawal, contentment, affiliation, neural toning down, and curiosity (e.g., Tops et al., 2009; Cools et al., 2010; Jepma et al., 2010; Veening et al., 2010; Lewis, 2011; Murphy et al., 2011).”
From Impulsive action: emotional impulses and their control (2014) · cites this paper as Jepma et al., 2010
The Introduction (page unavailable) describes a proposed role for the norepinephrine system in regulating exploration versus exploitation, which supports the claim’s curiosity-related component. The Discussion (page unavailable) reports that the study found no effect of increased norepinephrine on exploration or disengagement in its tasks. This paper does not support the sentence’s claims about oxytocin or the other listed motivational domains. (LLM, conf=0.86)
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Lin, H., Saunders, B., Hutcherson, C. A. C., & Inzlicht, M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/172122 · Cited by 6 · see citing works
Human complex exploration strategies are extended via noradrenaline-modulated heuristicsPreprint
Dubois, M., Habicht, J., Michely, J., Moran, R., Dolan, R. J., & Hauser, T. U. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.20.958025 · Cited by 4 · see citing works
Dijkstra, F. M., Zuiker, R. G. J. A., Siebenga, P. S., Leigh-Pemberton, R., Sun, L., Manthis, J. D., de Kam, M. L., Lin, R., Moltke, L. L., Rezendes, D., et al. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15229 · Cited by 2 · see citing works
Instructed Motivational States Bias Reinforcement Learning and Memory FormationPreprint
Sinclair, A. H., Wang, Y. C., & Adcock, R. A. (2022) · doi:10.31234/osf.io/z2rwf · Cited by 3 · see citing works
Mkrtchian, A., Qiu, Z., Abir, Y., Erdmann, T., Dercon, Q., Sedlinská, T., Browning, M. D., Costello, H., & Huys, Q. J. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.08.631868 · Cited by 2 · see citing works
A computational role for arousal in optimal inference
Nassar, M. R. (2012) · Scholarly Commons (University of Pennsylvania)
The effect of neuromodulators on cognitive control
van Bochove, M. E. (2014) · Ghent University Academic Bibliography (Ghent University)
Navigational strategy switching in ageing
Harris, M. A. (2014) · ERA
Environmental Conflict Modulates Pavlovian BiasPreprint
Priyanshu, P., & Ramakrishnan, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.22.696027
Impact of aging on human decision-making in ecological conditions
Aubert, J. D. S. (2023) · theses.fr (ABES) · doi:10.70675/f7143113zd412z4b5fza432z1032ef6ea209
- Authors
- Jepma
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2010
- Volume
- 4
- Pages
- 170-170
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC3009473
- OpenAlex
- W2129686766
- Cited by
- 45
- References
- 65
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 1 · 2014: 4 · 2012: 5
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion, other-oa)
- UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Decision Sciences › General Decision Sciences › Decision-Making and Behavioral Economics
- Keywords
- locus coeruleus, norepinephrine, exploration-exploitation balance, reboxetine, citalopram, task disengagement, exploratory behavior, gambling task, neuromodulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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