Molecular NeuroscienceResearch PaperA role for dopamine D2 receptors in reversal learning
Section snippets
Animals
All procedures involving animals were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at Columbia University and the New York State Psychiatric Institute. During the course of the study, the number of animals was kept to a minimum to ensure statistical validity and no procedures were performed that caused pain or severe discomfort. Adult male congenic C57BL/6J
ASST performance of D2 mutants and haloperidol- or clozapine-treated wild type
Fig. 1 illustrates the response accuracy (number of trials to criterion) of wild type, D2 mutants, and haloperidol-treated wild type. In wild type mice, a repeated measures ANOVA revealed significant differences when the number of trials to criterion was compared between test phases (F(4,40)=3.276; P=0.02). A post hoc Tukey–Kramer multiple comparisons test revealed that the number of trials to criterion needed to complete the EDS phase was significantly higher than that needed for either SD or
Discussion
The present study illustrates that knockout mice lacking dopamine D2 receptors and wild type mice treated chronically with the D2-like receptor blocker haloperidol have a deficit in the reversal phase of the ASST. In addition, both groups of mice exhibited decreased test-evoked expression of the transcription factor egr-2 in the vlOFC and IL/PrL subregions of the mPFC.
We show here that the reversal learning deficits of D2 mutants, their higher basal levels of egr-2 expression, and their
Acknowledgments
This work was supported by grants from the National Institutes of Health MH56123 and MH062185.
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2017, NeuroscienceCitation Excerpt :Regarding other dopamine receptor subtypes, low dopamine D2 receptor availability correlates with poor reversal learning in mice (Laughlin et al., 2011), monkeys (Groman et al., 2011) and humans (Jocham et al., 2009). Furthermore, D2 receptor gene deletion impairs reversal learning performance in mice (Kruzich and Grandy, 2004; Kruzich et al., 2006; De Steno and Schmauss, 2009), while either D2/D3 receptor agonists (quinpirole, 7-OH-DPAT) or antagonists (raclopride), impair spatial and olfactory reversals in rats (Boulougouris et al., 2009), monkeys (Smith et al., 1999; Lee et al., 2007) or healthy human volunteers (Mehta et al., 2001). These findings suggest that reversal learning depends upon an optimal balance of dopamine D2 receptor function (Izquierdo et al., 2012).
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