PUBLICATION
The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio)
- Authors
- Souders, C.L., Davis, R.H., Qing, H., Liang, X., Febo, M., Martyniuk, C.J.
- ID
- ZDB-PUB-191022-14
- Date
- 2019
- Source
- Brain and behavior 9(11): e01420 (Journal)
- Registered Authors
- Keywords
- MDPV, bath salts, behavioral screening, drug abuse, high-throughput
- MeSH Terms
-
- Animals
- Central Nervous System Stimulants/pharmacology*
- Dopamine/metabolism
- Dopamine Plasma Membrane Transport Proteins/drug effects
- Dopamine Plasma Membrane Transport Proteins/genetics
- Larva/drug effects
- Larva/metabolism
- Locomotion/drug effects*
- Oxidative Phosphorylation/drug effects
- Pyrrolidines/pharmacology*
- Receptors, Dopamine/drug effects
- Receptors, Dopamine/genetics
- Receptors, Dopamine D1/drug effects*
- Receptors, Dopamine D1/genetics
- Seizures/chemically induced
- Superoxide Dismutase-1/drug effects
- Superoxide Dismutase-1/metabolism
- Tyrosine 3-Monooxygenase/drug effects
- Tyrosine 3-Monooxygenase/genetics
- Zebrafish
- PubMed
- 31625691 Full text @ Brain Behav
Citation
Souders, C.L., Davis, R.H., Qing, H., Liang, X., Febo, M., Martyniuk, C.J. (2019) The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio). Brain and behavior. 9(11):e01420.
Abstract
Introduction Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone (beta-keto-amphetamine) derivative. Cathinones are a concern as drugs of abuse, as related street drugs such as methylenedioxypyrovalerone have garnered significant attention. The primary mechanism of action of cathinones is to inhibit reuptake transporters (dopamine and norepinephrine) in reward centers of the central nervous system.
Methods We measured bioenergetic, behavioral, and molecular responses to pyrovalerone (nM-µM) in zebrafish to evaluate its potential for neurotoxicity and neurological impairment.
Results Pyrovalerone did not induce any mortality in zebrafish larvae over a 3- and 24-hr period; however, seizures were prevalent at the highest dose tested (100 µM). Oxidative phosphorylation was not affected in the embryos, and there was no change in superoxide dismutase 1 expression. Following a 3-hr treatment to pyrovalerone (1-100 µM), larval zebrafish (6d) showed a dose-dependent decrease (70%-90%) in total distance moved in a visual motor response (VMR) test. We interrogated potential mechanisms related to the hypoactivity, focusing on the expression of dopamine-related transcripts as cathinones can modulate the dopamine system. Pyrovalerone decreased the expression levels of dopamine receptor D1 (~60%) in larval zebrafish but did not affect the expression of tyrosine hydroxylase, dopamine active transporter, or any other dopamine receptor subunit examined, suggesting that pyrovalerone may regulate the expression of dopamine receptors in a specific manner.
Discussion Further studies using zebrafish are expected to reveal new insight into molecular mechanisms and behavioral responses to cathinone derivates, and zebrafish may be a useful model for understanding the relationship between the dopamine system and bath salts.
Errata / Notes
This article is corrected by ZDB-PUB-220906-250 . Correction: https://onlinelibrary.wiley.com/doi/10.1002/brb3.2123 Corrects Article: https://onlinelibrary.wiley.com/doi/10.1002/brb3.1420
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping