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Behav Brain Res. 2018 Apr 2;341:129-134. doi: 10.1016/j.bbr.2017.12.029. Epub 2017 Dec 26.

Ventral tegmental area D2 receptor knockdown enhances choice impulsivity in a delay-discounting task in rats.

Author information

1
D'Youville College, Department of Biology and Mathematics, 320 Porter Avenue, Buffalo, NY 14201, USA.
2
Department of Pharmacology and Toxicology, Jacobs School of Medicine, University at Buffalo, SUNY, 102 Farber Hall, 3435 Main St., Buffalo, NY 14214, USA.
3
Department of Pharmacology and Toxicology, Jacobs School of Medicine, University at Buffalo, SUNY, 102 Farber Hall, 3435 Main St., Buffalo, NY 14214, USA. Electronic address: cebass@buffalo.edu.

Abstract

Impulsivity associated with abnormal dopamine (DA) function has been observed in several disorders, including addiction. Choice impulsivity is the preference for small, immediate rewards over larger rewards after a delay, caused by excessive discounting of future rewards. Addicts have abnormally high discount rates and prefer the smaller rewards sooner. While impulsivity has been inversely correlated with DA D2 receptor (D2R) availability in the midbrain and striatum, it is difficult to mechanistically link the two, due to the diverse neuroanatomical localization of D2Rs, which are found throughout the brain, in many types of neurons and neuronal subcompartments. To determine if ventral tegmental area (VTA) D2R hypofunction is linked to impulsivity, we knocked down D2 receptors from the VTA, using an adeno-associated viral (AAV) vector that delivers short hairpin RNAs (shRNA) targeted against the D2R. The D2R knockdown is restricted to neurons whose cell bodies reside in the VTA, leaving postsynaptic D2Rs intact in the striatum, prefrontal cortex, and other mesocorticolimbic structures. Rats were trained in a delay-discounting task to assess impulsive choice until a stable discounting curve was obtained, and then received bilateral VTA infusions of the D2R shRNA or a scrambled control virus. Over the next six weeks, the discounting curve of the VTA D2R knockdown rats shifted to the left, indicating a preference for the smaller, immediate reward, whereas the curve for control rats remained stable and unchanged. Together these results demonstrate that a decrease in VTA D2Rs enhances choice impulsivity.

KEYWORDS:

D2 autoreceptor; Delay-discounting; Impulsivity; Rat; VTA

PMID:
29287910
PMCID:
PMC5901913
DOI:
10.1016/j.bbr.2017.12.029
[Indexed for MEDLINE]
Free PMC Article

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