PUBLICATION
Integrative Roles of Dopamine Pathway and Calcium Channels Reveal a Link between Schizophrenia and Opioid Use Disorder
- Authors
- Thiagarajan, S.K., Mok, S.Y., Ogawa, S., Parhar, I.S., Tang, P.Y.
- ID
- ZDB-PUB-230226-69
- Date
- 2023
- Source
- International Journal of Molecular Sciences 24(4): (Journal)
- Registered Authors
- Ogawa, Satoshi
- Keywords
- addiction, behavior, calcium channel, domperidone, dopamine, morphine, schizophrenia, zebrafish
- MeSH Terms
-
- Animals
- Calcium Channels
- Dopamine/metabolism
- Dopaminergic Neurons/metabolism
- Morphine/pharmacology
- Opioid-Related Disorders*
- Schizophrenia*
- Zebrafish/metabolism
- PubMed
- 36835497 Full text @ Int. J. Mol. Sci.
Citation
Thiagarajan, S.K., Mok, S.Y., Ogawa, S., Parhar, I.S., Tang, P.Y. (2023) Integrative Roles of Dopamine Pathway and Calcium Channels Reveal a Link between Schizophrenia and Opioid Use Disorder. International Journal of Molecular Sciences. 24(4):.
Abstract
Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal. Drug-induced locomotion and social preference were assessed, while the level of dopamine and the number of dopaminergic neurons were quantified. In the brain tissue, the expression levels of genes associated with schizophrenia were measured. The effects of DMP and morphine were compared to vehicle control and MK-801, a positive control to mimic schizophrenia. Gene expression analysis revealed that α1C, α1Sa, α1Aa, drd2a, and th1 were up-regulated after 10 days of exposure to DMP and morphine, while th2 was down-regulated. These two drugs also increased the number of positive dopaminergic neurons and the total dopamine level but reduced the locomotion and social preference. The termination of morphine exposure led to the up-regulation of th2, drd2a, and c-fos during the withdrawal phase. Our integrated data implicate that the dopamine system plays a key role in the deficits in social behavior and locomotion that are common in the schizophrenia-like symptoms and opioid dependence.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping