Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens
Abstract
Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999-1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attention-deficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.
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Delay discounting is linked to dopamine and the function of dopamine-modulated fronto-striatal circuits.
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From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Adriani et al, 2009
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- Authors
- Adriani, W., Boyer, F., Gioiosa, L., Macrì, S., Dreyer, J.-L., & Laviola, G.
- Affiliations
- Istituto Superiore di Sanità (IT)
- University of Fribourg (CH)
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 159
- Issue
- 1
- Pages
- 47-58
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1994298252
- Cited by
- 97
- References
- 76
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 8 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 6 · 2012: 10
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- dopamine transporter, nucleus accumbens, impulsivity, sensation seeking, novelty seeking, delay discounting, risk-taking, self-control, attention deficit hyperactivity disorder, gambling addiction, dopaminergic tone, gene silencing
- MeSH terms
- Analysis of Variance, Animals, Choice Behavior, Conditioning, Operant, Exploratory Behavior, Gene Expression Regulation, Impulsive Behavior, Male, Mutation, Nucleus Accumbens, Probability, Reward, Risk-Taking, RNA, Messenger, Statistics as Topic, Lentivirus, Rats, Wistar, RNA, Small Interfering, Green Fluorescent Proteins, Dopamine Plasma Membrane Transport Proteins, Rats
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