PUBLICATION
Dopaminergic control of anxiety in young and aged zebrafish
- Authors
- Kacprzak, V., Patel, N.A., Riley, E., Yu, L., Yeh, J.J., Zhdanova, I.V.
- ID
- ZDB-PUB-170415-6
- Date
- 2017
- Source
- Pharmacology, biochemistry, and behavior 157: 1-8 (Journal)
- Registered Authors
- Zhdanova, Irina
- Keywords
- Aging, Anxiety, Cocaine, Dopamine, Dopamine receptors, Dopamine transporter, SCH23390, Sulpiride, Zebrafish
- MeSH Terms
-
- Aging/drug effects
- Aging/genetics
- Aging/metabolism*
- Animals
- Animals, Genetically Modified
- Anxiety/genetics
- Anxiety/metabolism*
- Base Sequence
- Dopamine/deficiency*
- Dopamine/genetics
- Dopamine Antagonists/pharmacology
- Dopamine Plasma Membrane Transport Proteins/deficiency*
- Dopamine Plasma Membrane Transport Proteins/genetics
- Male
- Receptors, Dopamine D1/genetics
- Receptors, Dopamine D1/metabolism*
- Receptors, Dopamine D2/genetics
- Receptors, Dopamine D2/metabolism*
- Zebrafish
- PubMed
- 28408289 Full text @ Pharmacol. Biochem. Behav.
Citation
Kacprzak, V., Patel, N.A., Riley, E., Yu, L., Yeh, J.J., Zhdanova, I.V. (2017) Dopaminergic control of anxiety in young and aged zebrafish. Pharmacology, biochemistry, and behavior. 157:1-8.
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 wildtype (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, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping