Integrative Roles of Dopamine Pathway and Calcium Channels Reveal a Link between Schizophrenia and Opioid Use Disorder

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 4088
• Main Authors: Thiagarajan, Siroshini K, Mok, Siew Ying, Ogawa, Satoshi, Parhar, Ishwar S, Tang, Pek Yee
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: addiction; Addictions; Animals; behavior; Brain; c-Fos protein; calcium channel; Calcium channels; Calcium Channels - metabolism; Cardiac glycosides; Cardiotonic agents; domperidone; Domperidone - administration & dosage; Domperidone - pharmacology; Dopamine; Dopamine - metabolism; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - pharmacology; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Drug abuse; Drug use; Drug withdrawal; Exposure; Fertilization; Gene expression; Genetic aspects; Genetic research; Larvae; Locomotion; Locomotion - drug effects; Lymphocytes T; Marijuana; Mental disorders; Metabolic Networks and Pathways; Morphine; Morphine - administration & dosage; Morphine - pharmacology; Neurons; Opioid-Related Disorders - metabolism; Opioids; Patient compliance; Phenols; Schizophrenia; Schizophrenia - metabolism; Social aspects; Social behavior; Substance use; Substance use disorder; Withdrawal; Zebrafish; Malaysia; calcium channel; addiction; domperidone; schizophrenia; zebrafish; behavior; dopamine; morphine
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24044088

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 , , , , and th1 were up-regulated after 10 days of exposure to DMP and morphine, while 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 , , and 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.