PUBLICATION
Dopamine-neurotransmission and nociception in zebrafish: An anti-nociceptive role of dopamine receptor drd2a
- Authors
- van Reij, R.R.I., Salmans, M.M.A., Eijkenboom, I., van den Hoogen, N.J., Joosten, E.A.J., Vanoevelen, J.M.
- ID
- ZDB-PUB-210924-7
- Date
- 2021
- Source
- European Journal of Pharmacology 912: 174517 (Journal)
- Registered Authors
- Keywords
- DRD2, Danio rerio, Morpholino, Pain, Pharmacology, Quinpirole
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects
- Behavior, Animal/physiology
- Dopamine/physiology*
- Hot Temperature
- Models, Animal
- Morpholinos/pharmacology
- Nociception/drug effects
- Nociception/physiology*
- Quinpirole/pharmacology
- Receptors, Dopamine D2/agonists
- Receptors, Dopamine D2/genetics*
- Receptors, Dopamine D2/physiology*
- Synaptic Transmission/drug effects
- Synaptic Transmission/physiology*
- Zebrafish
- PubMed
- 34555394 Full text @ Eur. J. Pharmacol.
Citation
van Reij, R.R.I., Salmans, M.M.A., Eijkenboom, I., van den Hoogen, N.J., Joosten, E.A.J., Vanoevelen, J.M. (2021) Dopamine-neurotransmission and nociception in zebrafish: An anti-nociceptive role of dopamine receptor drd2a. European Journal of Pharmacology. 912:174517.
Abstract
Dopamine (DA) is an important modulator in nociception and analgesia. Spinal DA receptors are involved in descending modulation of the nociceptive transmission. Genetic variations within DA neurotransmission have been associated with altered pain sensitivity and development of chronic pain syndromes. The variant rs6277 in dopamine receptor 2 a (drd2a) has been associated with a decreased D2 receptor availability and increased nociception. The aim of this study is to further characterize the role of DA neurotransmission in nociception and the anti-nociceptive function of drd2a. The phenotype caused by rs6277 was modelled in zebrafish larvae using morpholino's and the effect on nociception was tested using a validated behavioural assay. The anti-nociceptive role of drd2a was tested using pharmacological intervention of D2 agonist Quinpirole. The experiments demonstrate that a decrease in drd2a expression results in a pro-nociceptive behavioural phenotype (P = 0.016) after a heat stimulus. Furthermore, agonism of drd2a with agonist Quinpirole (0.2 μM) results in dose-dependent anti-nociception (P = 0.035) after a heat stimulus. From these results it is concluded that the dopamine receptor drd2a is involved in anti-nociceptive behaviour in zebrafish. The model allows further screening and testing of genetic variation and treatment involved in nociception.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping