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Mesocortical dopamine modulation of executive functions: beyond working memory

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Abstract

Rationale

Dopamine (DA) neurotransmission in the prefrontal cortex (PFC) is known to play an essential role in mediating executive functions such as the working memory. DA exerts these effects by acting on D1 receptors because blockade or stimulation of these receptors in the PFC can impair performance on delayed response tasks. However, comparatively less is known about dopaminergic mechanisms that mediate other executive functions regulated by the PFC. Furthermore, the functional importance of other DA receptor subtypes that reside on PFC neurons (D2 and D4) is unclear.

Objectives

This review will summarize previous findings and previously unpublished data addressing the contribution of PFC DA to higher-order cognition. We will compare the DA receptor mechanisms, which regulate executive functions such as working memory, behavioral flexibility, and decision-making.

Results and conclusions

Whereas PFC D1 receptor activity is of primary importance in working memory, D1 and D2 receptors act in a cooperative manner to facilitate behavioral flexibility. We note that the principle of the “inverted U-shaped” function of D1 receptor activity mediating working memory does not necessarily apply to other PFC functions. DA in different subregions of the PFC also mediates decision-making assessed with delay discounting or effort-based procedures, and we report that D1, D2, and D4 receptors in the medial PFC contribute to decision-making when animals must bias the direction of behavior to avoid aversive stimuli, assessed with a conditioned punishment procedure. Thus, mesocortical DA modulation of distinct executive functions is subserved by dissociable profiles of DA receptor activity in the PFC.

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Acknowledgements

Some of the research reviewed in this article was supported by a Natural Sciences and Engineering Research Council of Canada Discovery Grant and National Alliance for Research on Schizophrenia and Depression Young Investigator Award to SBF. The previously unpublished study presented here was supported by an operating grant from the Canadian Institutes of Health Research (CIHR) to SBF. SBF is a CIHR New Investigator and a Michael Smith Foundation for Health Research Scholar. The authors would like to thank Sarah Thompson for her assistance with behavioral testing.

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Authors and Affiliations

  1. Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T1Z4, Canada

    Stan B. Floresco & Orsolya Magyar

  2. Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T1Z4, Canada

    Stan B. Floresco & Orsolya Magyar

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  1. Stan B. Floresco
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  2. Orsolya Magyar
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Correspondence to Stan B. Floresco.

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Floresco, S.B., Magyar, O. Mesocortical dopamine modulation of executive functions: beyond working memory. Psychopharmacology 188, 567–585 (2006). https://doi.org/10.1007/s00213-006-0404-5

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