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Pharmacol Biochem Behav. 2017 Jun;157:1-8. doi: 10.1016/j.pbb.2017.01.005. Epub 2017 Apr 10.

Dopaminergic control of anxiety in young and aged zebrafish.

Author information

1
Boston University School of Medicine, Lab of Sleep and Circadian Physiology, R-911, 72 E. Concord St., Boston, MA 02118, United States. Electronic address: veekaz@bu.edu.
2
Boston University School of Medicine, Lab of Sleep and Circadian Physiology, R-911, 72 E. Concord St., Boston, MA 02118, United States. Electronic address: neil92@bu.edu.
3
Boston University School of Medicine, Lab of Sleep and Circadian Physiology, R-911, 72 E. Concord St., Boston, MA 02118, United States. Electronic address: elizabeth_riley@hms.harvard.edu.
4
Boston University School of Medicine, Lab of Sleep and Circadian Physiology, R-911, 72 E. Concord St., Boston, MA 02118, United States. Electronic address: yulili@bu.edu.
5
Massachusetts General Hospital, Cardiovascular Research Center, 149 13th St., 4.217, Charlestown, MA 02129, United States. Electronic address: JYEH1@mgh.harvard.edu.
6
Boston University School of Medicine, Lab of Sleep and Circadian Physiology, R-911, 72 E. Concord St., Boston, MA 02118, United States. Electronic address: zhdanova@bu.edu.

Abstract

Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wild type (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed. We established that DAT-KO results in a chronic anxiety-like state, seen as an increase in bottom-dwelling and thigmotaxis. Similar effects were produced by aging and acute cocaine administration, both leading to reduction in DAT mRNA abundance (qPCR). Inhibition of D1 activity counteracted the anxiety-like effects associated with DAT deficit, independent of its origin. Inhibition of D2/D3 receptors reduced anxiety in young DAT-KO, and enhanced the anxiogenic effects of cocaine in WT, but did not affect aged WT or DAT-KO fish. These findings provide new evidence that the dopaminergic system plays a critical role in anxiety-like states, and suggest that adult zebrafish provide a sensitive diurnal vertebrate model for elucidating the molecular mechanisms of anxiety and a platform for anxiolytic drug screens.

KEYWORDS:

Aging; Anxiety; Cocaine; Dopamine; Dopamine receptors; Dopamine transporter; SCH23390; Sulpiride; Zebrafish

PMID:
28408289
PMCID:
PMC5505502
DOI:
10.1016/j.pbb.2017.01.005
[Indexed for MEDLINE]
Free PMC Article

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