The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Enhancement of Spatial Reversal Learning by 5-HT2CReceptor Antagonism Is Neuroanatomically Specific
Open accessAbstract
We have recently demonstrated that systemic administration of 5-HT(2C) and 5-HT(2A) receptor antagonists significantly enhanced and impaired spatial reversal learning, respectively. In this study, the role of 5-HT(2C) and 5-HT(2A) receptor subtypes in the mediation of these opposing effects was further investigated with respect to neuroanatomical specificity. The roles of 5-HT(2C) and 5-HT(2A) receptors were examined within some of the brain regions implicated in cognitive flexibility, namely the orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and nucleus accumbens (NAc), by means of targeted infusions of selective 5-HT(2C) and 5-HT(2A) receptor antagonists (SB 242084 and M100907, respectively). Intra-OFC 5-HT(2C) receptor antagonism produced dose-dependent effects similar to those of systemic administration, i.e., improved spatial reversal learning by reducing the number of trials (all doses: 0.1, 0.3, and 1.0 microg) and perseverative errors to criterion (0.3 and 1.0 microg) compared with controls. However, the highest dose (1.0 microg) showed a nonselective effect, as it also affected retention preceding the reversal phase and decreased learning errors. Intracerebral infusions of SB 242084 into the mPFC or NAc produced no significant effects on any behavioral measures. Similarly, no significant differences were observed with intra-OFC, -mPFC, or -NAc infusions of M100907. These data suggest that the improved performance in reversal learning observed after 5-HT(2C) receptor antagonism is mediated within the OFC. These data also bear on the issue of whether 5-HT(2C) receptor antagonism within the OFC might help elucidate the biological substrate of obsessive-compulsive disorder, offering the potential for therapeutic application.
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“In reversal tasks in which action-outcome contingencies were switched, lesions or pharmacological manipulations of serotonin neurons also resulted in impairments of adaptive behavior at the time of reversal.37–41”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [39]
In the citing paper
“Our findings and conceptual framework, including the effect on learning from worse-than-expected outcomes, are consistent with previous observations and manipulations of serotonin neuron activity.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [39]
In the citing paper
“Prior research demonstrates that serotonin neurons modulate flexible behavior in changing environments.33,37–42”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [39]
In the citing paper
“Specifically, lesioned animals continued to make the previously rewarded action.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [39]
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Citations
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · cited 3×
“The coordinates used were as follows (Paxinos and Watson, 1998): OFC: anteroposterior (AP), 3.”
InfluentialAn Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803 · cited 1×
“Without this top-down cognitive control, behavior controlled by other cortical and subcortical regions is more likely to be inflexible, dependent on simple sensory motor associations or habits (Miller and Cohen, 2001).”
BackgroundAChE-stained horizontal sections of the rat brain in stereotaxic coordinates
Paxinos, G., WATSON, C. R. R., & Emson, P. C. (1980) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(80)90021-7 · Cited by 4,501
Dissociation in prefrontal cortex of affective and attentional shifts
Dias, R., Robbins, T. W., & Roberts, A. C. (1996) · Nature · doi:10.1038/380069a0 · Cited by 1,527 · cited 3×
“The medial region of the PFC (mPFC) has been shown to mediate behavioral flexibility in attentional set-shifting tasks, requiring the updating of attentional biases or rules (Owen et al., 1991; Dias et al., 1996; Birrell and Brown, 2000; Ragozzino and Kesner, 2001).”
BackgroundSelf-citationMedial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat
Birrell, J. M., & Brown, V. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04320.2000 · Cited by 1,421 · cited 1×
“The medial region of the PFC (mPFC) has been shown to mediate behavioral flexibility in attentional set-shifting tasks, requiring the updating of attentional biases or rules (Owen et al., 1991; Dias et al., 1996; Birrell and Brown, 2000; Ragozzino and Kesner, 2001).”
BackgroundRolls, E. T., Hornak, J., Wade, D., & McGrath, J. (1994) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.57.12.1518 · Cited by 1,005 · cited 2×
“Neuroanatomically speaking, converging evidence from a plethora of studies has implicated the orbitofrontal cortex (OFC) in efficient reversal learning, as damage to this region produces selective reversal deficits [human (Rolls et al., 1994; Hornak et al., 2004), monkey (Iversen and Mishkin, 1970; Jones and Mishkin,…”
BackgroundAmat, J., Baratta, M. V., Paul, E., Bland, S. T., Watkins, L. R., & Maier, S. F. (2005) · Nature Neuroscience · doi:10.1038/nn1399 · Cited by 931 · cited 2×
“If this regulation also results from descending influences from mPFC (Amat et al., 2005), then this may imply a descending modulation of the dorsal raphé by OFC 5-HT2C receptors.”
BackgroundWinstanley, C. A., Eagle, D. M., & Robbins, T. W. (2006) · Clinical Psychology Review · doi:10.1016/j.cpr.2006.01.001 · Cited by 893 · cited 2×
“(Robbins, 2000; Chudasama and Robbins, 2004; Winstanley et al., 2006).”
BackgroundInfluentialLimbic lesions and the problem of stimulus--reinforcement associations.
Jones, B., & Mishkin, M. (1972) · Experimental Neurology · doi:10.1016/0014-4886(72)90030-1 · Cited by 864 · cited 2×
“, 2004), monkey (Iversen and Mishkin, 1970; Jones and Mishkin, 1972; Dias et al., 1996; Clarke et al., 2008), rat (Schoenbaum et al.”
BackgroundIversen, S., & Mishkin, M. (1970) · Experimental Brain Research · doi:10.1007/bf00237911 · Cited by 767 · cited 2×
“, 2004), monkey (Iversen and Mishkin, 1970; Jones and Mishkin, 1972; Dias et al., 1996; Clarke et al., 2008), rat (Schoenbaum et al.”
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Items 101–137 of 137
Clueless about cues: the impact of reward-paired cues on decision making under uncertainty
Winstanley, C. A., & Hynes, T. J. (2021) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2021.07.001 · Cited by 15
Feng, Y.-Y., Bromberg-Martin, E. S., & Monosov, I. E. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114341 · Cited by 18
Meneses, A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-408139-0.00002-x · Cited by 12
Hervig, M. E.-S., Piilgaard, L., Božič, T., Alsiö, J., & Robbins, T. W. (2020) · Psychology & Neuroscience · doi:10.1037/pne0000221 · Cited by 11
“This dose has been used in lOFC in a previous reversal learning study with no effects (Boulougouris & Robbins, 2010) and in the mPFC with effects on compulsivity (Mora et al., 2018).”
BackgroundMethodInfluentialNilsson, S. R. O., Somerville, E. M., & Clifton, P. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077762 · Cited by 12
“The observed effect of SB242084 in the perseverance test is in agreement with previous studies indicating that acute 5-HT2CR antagonism attenuates perseverative responding [15,30].”
BackgroundMethodResultInfluentialRussell, B., Hrelja, K. M., Adams, W. K., Zeeb, F. D., Taves, M. D., Kaur, S., Soma, K. K., & Winstanley, C. A. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.114000 · Cited by 10
Wright, A., Zapata, A. G., Baumann, M. H., Elmore, J. S., Hoffman, A. F., & Lupica, C. R. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw312 · Cited by 11
Cognitive inflexibility, obsessive-compulsive symptoms and traits and poor post-pandemic adjustment
Frota Lisboa Pereira de Souza, A. M., Pellegrini, L., & Fineberg, N. A. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104073 · Cited by 8
“Ketamine (Nikiforuk and Popik, 2014), psilocybin (Torrado Pacheco et al., 2023), experimental selective 5HT2c antagonists (Boulougouris and Robbins, 2010), and a group II metabotropic glutamate receptor (mGluR) positive allosteric modulator (Nikiforuk et al., 2010) have also been tested in animal…”
Hatakama, H., Asaoka, N., Nagayasu, K., Shirakawa, H., & Kaneko, S. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108926 · Cited by 9
Nucleus Reuniens: Circuitry, Function, and Dysfunction
Vertes, R. P., Linley, S. B., & Viena, T. D. (2022) · Neuromethods · doi:10.1007/978-1-0716-2631-3_4 · Cited by 8
Ochoa, J. G., Stolyarova, A., Kaur, A., Hart, E. E., Bugarin, A., & Izquierdo, A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00155 · Cited by 8
“…differences, it appears that BLA is selectively important in updating responses to changes in reward value (Coleman-Mesches et al., 1996; Baxter and Murray, 2002; Liao and Chuang, 2003; Belova et al., 2008) and sensitivity to negative feedback (Rudebeck and Murray, 2008; Izquierdo et al., 2013).”
Dougherty, J. P., & Oristaglio, J. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.04.002 · Cited by 8
Dorsal raphe neurons signal integrated value during multi-attribute decision-makingPreprint
Feng, Y.-Y., Bromberg-Martin, E. S., & Monosov, I. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.17.553745 · Cited by 6
Serotonin and cognitive flexibility
Nilsson, S. R. O., Phillips, B. U., Axelsson, S. F. A., & Alsiö, J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813323-1.00008-6 · Cited by 7
Phillips, B. U., & Robbins, T. W. (2020) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-444-64125-0.00031-1 · Cited by 5
Firing patterns of serotonin neurons underlying cognitive flexibilityPreprint
Matias, S., Lottem, E., Dugué, G. P., & Mainen, Z. F. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/059758 · Cited by 5
Absence of sex differences in serotonergic control of orbitofrontal cortex neuronal activity
Mooney, K., Hoffman, A. F., & Lupica, C. R. (2025) · Scientific Reports · doi:10.1038/s41598-025-11208-2 · Cited by 4
“Both in pharmacological studies 13–15 and in studies using 5-HT transporter knockout rodents 16,17 disruptions to 5-HT circuitry have been found to alter OFC-dependent behaviors.”
Kosted, R., Doss, M. K., Donegan, J. J., Cisler, J. M., & Fonzo, G. A. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106788 · Cited by 3
Gregersen, A. T., Whelan, T. P., Golden, C. T., Blackmore, T., & Palner, M. (2026) · Psychedelic Medicine · doi:10.1177/28314425251386879 · Cited by 2
The Role of Serotonin on Attentional Processes and Executive Functioning: Focus on 5-HT2C Receptors
Tsaltas, E., & Boulougouris, V. (2010) · The Receptors · doi:10.1007/978-1-60761-941-3_23 · Cited by 2
“With permission). (d) Effects of intra-OFC infusions of SB 242084 on incorrect responses during spatial reversal learning (Adapted from Boulougouris and Robbins 2010 .”
BackgroundDissecting Motivation: Translational Approaches and Clinical Implications
Avlar, B. (2016) · doi:10.7916/d8df6r7r · Cited by 2
Boillot, M., ter Horst, J., López, J. R., Fazio, I. D., Steens, I. L. M., Cohen, M. X., & Homberg, J. R. (2024) · Cerebral Cortex · doi:10.1093/cercor/bhae334 · Cited by 1
Touchscreen Assessment of Motivation and Reinforcement-Related Choice Behaviour in Mice
Phillips, B. U. (2017) · Apollo (University of Cambridge) · doi:10.17863/cam.24393 · Cited by 1
Zhang, Y. (2011) · University Library - University of Saskatchewan (University of Saskatchewan)
Baker, T. W. (2013) · QSpace (Queen's University Library)
5HT2A Receptor Antagonist Treatment for Repetitive Behaviors and Restricted Interests in BTBR Mice
Amodeo, D. A. (2015) · Figshare
Rendall, A. R. (2017) · OpenCommons at University of Connecticut (University of Connecticut)
5-HT2A/2B/2C Receptors, Memory and Therapeutic Targets
Meneses, A., Nieto-Vera, R., & Anaya-Jiménez, R. M. (2018) · Springer eBooks · doi:10.1007/978-3-319-70474-6_11
Zhukovsky, P. (2019) · Apollo (University of Cambridge) · doi:10.17863/cam.52099
Unexpected Uncertainty in Adaptive Learning
Șandru, A. R. (2022) · Wittgenstein-Studien · doi:10.1515/witt-2022-0010
(2014) · Elsevier eBooks · doi:10.1016/b978-0-12-800836-2.00022-2
Bhogegowda, K. K. H., Niketh, S., Thyloor, R., & Kolgi, R. R. (2024) · Research in Biotechnology · doi:10.25081/rib.2024.v15.9081
Asraf, K., & Gaisler‐Salomon, I. (2025) · Biomolecules · doi:10.3390/biom15081154
“In other studies, both systemic [122] or OFC-specific [123] 5-HT2C receptor blockade improved reversal learning.”
Tuite, K. M., Ouellette, M. C., Girotti, M., & Morilak, D. A. (2026) · Neurobiology of Stress · doi:10.1016/j.ynstr.2026.100789
“Error analysis: In addition to Trials to Criterion (TTC), we also analyzed perseverative errors, defined as 3 or more incorrect choices in a row, representing persistent responding to the previously positive cue (Boulougouris and Robbins, 2010).”
A push–pull gut–brain signal regulates flexible learning in Caenorhabditis elegans
Liu, H., Sun, Y., Jiang, C., Dong, N., Yang, Y. C., Zhu, Y., Qin, R., Jia, H., Zhang, K., Li, H. C., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2604270123
BindingDB (2019) · UC San Diego · doi:10.7270/q2377c5d
Metadata
- Authors
- Boulougouris, V., & Robbins, T. W.
- Affiliations
- University of Cambridge (GB)
- ORCID
- Robbins, Trevor W.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-01-20
- Volume
- 30
- Issue
- 3
- Pages
- 930-938
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6633094
- OpenAlex
- W2090419097
- Cited by
- 136
- References
- 60
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 2 · 2018: 7 · 2017: 10 · 2016: 10 · 2015: 14 · 2014: 10 · 2013: 16 · 2012: 7
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (076274/4/Z/04/Z, 076274/Z/04/Z)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- 5-HT2C receptor antagonism, 5-HT2A receptor antagonism, spatial reversal learning, cognitive flexibility, orbitofrontal cortex, medial prefrontal cortex, nucleus accumbens, SB242084, M100907, perseverative errors, obsessive-compulsive disorder
- MeSH terms
- Aminopyridines, Analysis of Variance, Animals, Brain, Brain Mapping, Conditioning, Operant, Dose-Response Relationship, Drug, Fluorobenzenes, Indoles, Male, Piperidines, Reinforcement Schedule, Reversal Learning, Serotonin Antagonists, Space Perception, Time Factors, Receptor, Serotonin, 5-HT2A, Receptor, Serotonin, 5-HT2C, Rats, Serotonin 5-HT2 Receptor Antagonists
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