D2 receptors and cognitive flexibility in marmosets: tri-phasic dose-response effects of intra-striatal quinpirole on serial reversal performance.
Springer Science and Business Media LLC
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Horst, N., Jupp, B., Roberts, A., & Robbins, T. (2019). D2 receptors and cognitive flexibility in marmosets: tri-phasic dose-response effects of intra-striatal quinpirole on serial reversal performance.. Neuropsychopharmacology, 44 (3), 564-571. https://doi.org/10.1038/s41386-018-0272-9
Behavioral flexibility, which allows organisms to adapt their actions in response to environmental changes, is impaired in a number of neuropsychiatric conditions, including obsessive-compulsive disorder and addiction. Studies in human subjects and monkeys have reported correlations between individual differences in dopamine D2-type receptor (D2R) levels in the caudate nucleus and performance in a discrimination reversal task, in which established contingent relationships between abstract stimuli and rewards (or punishments) are reversed. Global genetic deletion of the D2R in mice disrupts reversal performance, indicating a likely causal role for this receptor in supporting flexible behaviors. To directly examine the specific role of caudate D2-type receptors in reversal performance, the D2/3/4R agonist quinpirole was infused via chronic indwelling cannulae into the medial caudate of male and female marmoset monkeys performing a touchscreen-based serial discrimination reversal task. Given prior evidence for dose-dependent effects of quinpirole and other dopaminergic drugs, a full dose-response curve was established. Individually, marmosets displayed marked differences in behavioral sensitivity to specific doses of intra-caudate quinpirole. Collectively, they exhibited a behaviorally specific bi-phasic deficit in reversal learning, being consistently impaired at both relatively low and high doses of quinpirole. However, intermediate doses of intra-caudate quinpirole produced significant improvement in reversal performance. These data support previous human and monkey neuroimaging studies by providing causal evidence of a U-shaped function describing how dopamine modulates cognitive flexibility in the primate striatum.
Caudate Nucleus, Animals, Callithrix, Quinpirole, Receptors, Dopamine D2, Dopamine Agonists, Behavior, Animal, Discrimination Learning, Reversal Learning, Serial Learning, Dose-Response Relationship, Drug, Female, Male
Wellcome Trust (104631/Z/14/Z)
Medical Research Council (MR/J012084/1)
Medical Research Council (G1000183)
Medical Research Council (G0001354)
External DOI: https://doi.org/10.1038/s41386-018-0272-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286708
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/