Research article summary (published May 2009):

A role for dopamine D2 receptors in reversal learning.

Full Abstract

Reversal learning has been shown to require intact serotonergic innervation of the forebrain neocortex. Whether dopamine acting through D2 receptors plays a complementary role in this anatomic area is still unclear. Here we show that mice lacking dopamine D2 receptors exhibited significantly impaired performance in the reversal learning phase of an attention-set-shifting task (ASST) and that wild type mice treated chronically with the D2-like receptor antagonist haloperidol exhibited the same cognitive deficit. The test-phase-specific deficits of D2 mutants and haloperidol-treated mice were also accompanied by deficits in the induction of expression of early growth response gene 2 (egr-2), a regulatory transcription factor previously shown to be selectively induced in the ventrolateral orbital frontal cortex and the pre- and infralimbic medial prefrontal cortex of ASST-tested mice. D2-receptor knockout mice and haloperidol-treated wild type, however, exhibited lower egr-2 expression in these anatomic regions after completion of an ASST-test phase that required reversal learning but not after completion of set-shifting phases without rule reversals. In contrast, mice treated chronically with clozapine, an atypical neuroleptic drug with lower D2-receptor affinity and broader pharmacological effects, had deficits in compound discrimination phases of the ASST, but also these deficits were accompanied by lower egr-2 expression in the same anatomic subregions. Thus, the findings indicate that egr-2 expression is a sensitive indicator of test-phase-specific performance in the ASST and that normal function of D2 receptors in subregions of the orbital frontal and the medial prefrontal cortex is required for cognitive flexibility in tests involving rule reversals.

Author information

Author/s: De Steno, D A (DA); Schmauss, C (C);

Affiliation: Department of Pharmacology, Columbia University, New York, NY 10032, USA.

Grants: MH062185 (Agency:NIMH NIH HHS) ; MH56123 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2009-Aug; vol 162 (issue 1) : pp 118-27

Dates: Created 2009/06/09; Completed 2009/08/25;

PMID: 19401217, status: MEDLINE (last retrieval date: 8/25/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Clozapine - administration & dosage Cognition - drug effects; physiology Dopamine Antagonists - administration & dosage Early Growth Response Protein 2 - genetics; metabolism Frontal Lobe - drug effects; metabolism Gene Expression - drug effects; physiology Haloperidol - administration & dosage Learning Disorders - chemically induced; metabolism Male

Male Mice Mice, Inbred C57BL Mice, Knockout Neuropsychological Tests Neurotransmitter Agents - administration & dosage Prefrontal Cortex - drug effects; metabolism RNA, Messenger - metabolism Receptors, Dopamine D2 - antagonists & inhibitors; genetics; metabolism Reversal Learning - drug effects; physiology

Associated Chemicals: Dopamine Antagonists (0) ; Early Growth Response Protein 2 (0) ; Egr2 protein, mouse (0) ; Neurotransmitter Agents (0) ; RNA, Messenger (0) ; Receptors, Dopamine D2 (0) ; Haloperidol (52-86-8) ; Clozapine (5786-21-0)

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