Abstract
Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra-NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.
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Acknowledgements
This study was funded by the Wellcome Trust (076274/2/04/2), MRC (G0600196, G0401068), IMAGEN under the European Communities Sixth Framework Programme (LSHM-CT-2007-037286), and the National Institute on Drug Abuse (Intramural Research Program). MB was supported by a ‘Fondation pour la Recherche Médicale’ fellowship. The authors thank Alan G Lyon for technical assistance.
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TWR discloses consultancy for Cambridge Cognition, Pfizer, E Lilly Inc., Wyeth, GlaxoSmithKline, and Roche and holds share options in Cambridge Cognition and Allon Therapeutics. MB, DB, RM, DT, AC, VB, BC, AN, BE, and JD have no disclosures.
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Besson, M., Belin, D., McNamara, R. et al. Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens. Neuropsychopharmacol 35, 560–569 (2010). https://doi.org/10.1038/npp.2009.162
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DOI: https://doi.org/10.1038/npp.2009.162
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