Dissociation of prefrontal cortex and nucleus accumbens dopaminergic systems in conditional learning in rats
Open accessAbstract
There is converging evidence that the prefrontal and mesolimbic dopaminergic (DAergic) systems are involved in the performance of a variety of tasks that require the use of contextual, or task-setting, information to select an appropriate response from a number of candidate responses. Performance on tasks of this nature are impaired in schizophrenia and in rats exposed to psychotomimetics; impairments that are often attenuated by administration of dopamine (DA) antagonists. Rats were trained on either a complex instrumental discrimination task, that required the use of task-setting cues, or a simple discrimination task that did not. Following training, microdialysis probes were implanted unilaterally in either the medial prefrontal cortex (mPFC) or nucleus accumbens (NAc) and samples were collected in freely moving animals during a behavioural test session. In Experiment 1, we found no difference in levels of DA in the mPFC of rats while they were performing the two discrimination tasks. Rats that performed the complex task did, however, show significantly higher mPFC DA levels relative to rats in the simple discrimination condition following the end of the behavioural test session. In Experiment 2, rats performing the conditional discrimination showed lower levels of DA in the NAc compared to the simple discrimination group both during the test session and after it. These results provide direct evidence that conditional discrimination tasks engage frontal and mesolimbic DAer…
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Conditional discrimination tasks engage frontal and meso-limbic dopaminergic systems, with dopamine increased in the prefrontal cortex and reduced in the nucleus accumbens region of the striatum in wildtype rats performing this task.
“George and colleagues [44] have demonstrated direct evidence that conditional discrimination tasks engage frontal and meso-limbic dopaminergic systems, with dopamine increased in the prefrontal cortex and reduced in the nucleus accumbens region of the striatum in wildtype rats performing this task.”
Cyfip1+/− animals proved prone to behavioural inflexibility in a conditional discrimination paradigm known to engage fronto-striatal circuitry.
“Alongside the disordered network dynamics centred on the nucleus accumbens and its connections, Cyfip1+/− animals proved prone to behavioural inflexibility in a conditional discrimination paradigm, known to engage fronto-striatal circuitry [44].”
Eight days of training is long enough for WT rats to successfully acquire the discrimination.
“The animals in the current study were trained blind to genotype for eight days on the discrimination task—which we have previously shown to be long enough for WT rats to successfully acquire the discrimination [44, 49].”
These sample sizes were utilised on the basis of previous published research and pilot studies.
“These sample sizes were utilised on the basis of previous published research [11, 44, 45] and pilot studies.”
The conditional discrimination task used here has been shown to recruit meso-limbic dopaminergic systems in the frontal cortex and nucleus accumbens.
“The conditional discrimination task used here has been shown to recruit meso-limbic dopaminergic systems in the frontal cortex and nucleus accumbens [44], and is highly sensitive to dopamine dysfunction [94, 95].”
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Feeding and hypothalamic stimulation increase dopamine turnover in the accumbens
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Duncan, N. W., Wiebking, C., Tiret, B., Marjańska, M., Hayes, D. J., Lyttleton, O., Doyon, J., & Northoff, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060312 · Cited by 95 · see citing works
Haddon, J. E., Titherage, D., Heckenast, J. R., Carter, J., Owen, M. J., Hall, J., Wilkinson, L. S., & Jones, M. W. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02969-x · Cited by 6 · see citing works
“George and colleagues [44] have demonstrated direct evidence that conditional discrimination tasks engage frontal and meso-limbic dopaminergic systems, with dopamine increased in the prefrontal cortex and reduced in the nucleus accumbens region of the striatum in wildtype rats performing this task.”
BackgroundMethodInfluential
- Authors
- George, D. N., Jenkins, T. A., & Killcross, S.
- Affiliations
- University of Hull (GB)
- RMIT University (AU)
- UNSW Sydney (AU)
- Corresponding author
- George, David N.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 225
- Issue
- 1
- Pages
- 47-55
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2124030834
- Cited by
- 8
- References
- 4
- Citations by year
- 2024: 1 · 2017: 1 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- prefrontal cortex, nucleus accumbens, dopaminergic system, conditional discrimination, cognitive control, schizophrenia, mesolimbic dopamine system, dopamine release, psychotomimetics
- MeSH terms
- Analysis of Variance, Animals, Chromatography, High Pressure Liquid, Conditioning, Operant, Discrimination, Psychological, Dopamine, Electrochemistry, Male, Nucleus Accumbens, Prefrontal Cortex, Rats
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