Selective chemogenetic inactivation of corticoaccumbal projections disrupts trait choice impulsivity.

Autor: Wenzel JM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. jenwenzel@sandiego.edu.; Department of Psychological Sciences, University of San Diego, San Diego, CA, 92110, USA. jenwenzel@sandiego.edu., Zlebnik NE; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. natalie.zlebnik@medsch.ucr.edu.; Division of Biomedical Sciences, University of California, Riverside School of Medicine, Riverside, CA, 92521, USA. natalie.zlebnik@medsch.ucr.edu., Patton MH; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; St. Jude Children's Research Hospital, Memphis, TN, 38105, USA., Smethells JR; Hennepin Healthcare Research Institute, Minneapolis, MN, 55404, USA., Ayvazian VM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Dantrassy HM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Zhang LY; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Mathur BN; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Cheer JF; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2023 Nov; Vol. 48 (12), pp. 1821-1831. Date of Electronic Publication: 2023 May 19.
DOI: 10.1038/s41386-023-01604-5
Abstrakt: Impulsive choice has enduring trait-like characteristics and is defined by preference for small immediate rewards over larger delayed ones. Importantly, it is a determining factor in the development and persistence of substance use disorder (SUD). Emerging evidence from human and animal studies suggests frontal cortical regions exert influence over striatal reward processing areas during decision-making in impulsive choice or delay discounting (DD) tasks. The goal of this study was to examine how these circuits are involved in decision-making in animals with defined trait impulsivity. To this end, we trained adolescent male rats to stable behavior on a DD procedure and then re-trained them in adulthood to assess trait-like, conserved impulsive choice across development. We then used chemogenetic tools to selectively and reversibly target corticostriatal projections during performance of the DD task. The prelimbic region of the medial prefrontal cortex (mPFC) was injected with a viral vector expressing inhibitory designer receptors exclusively activated by designer drugs (Gi-DREADD), and then mPFC projections to the nucleus accumbens core (NAc) were selectively suppressed by intra-NAc administration of the Gi-DREADD actuator clozapine-n-oxide (CNO). Inactivation of the mPFC-NAc projection elicited a robust increase in impulsive choice in rats with lower vs. higher baseline impulsivity. This demonstrates a fundamental role for mPFC afferents to the NAc during choice impulsivity and suggests that maladaptive hypofrontality may underlie decreased executive control in animals with higher levels of choice impulsivity. Results such as these may have important implications for the pathophysiology and treatment of impulse control, SUDs, and related psychiatric disorders.
(© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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