PUBLICATION
Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish
- Authors
- Khor, B.S., Amar Jamil, M.F., Adenan, M.I., and Chong Shu-Chien, A.
- ID
- ZDB-PUB-120110-6
- Date
- 2011
- Source
- PLoS One 6(12): e28340 (Journal)
- Registered Authors
- Keywords
- Morphine, Drug addiction, Zebrafish, Fishes, Substance addiction, Hydrocortisone, Swimming, Animal behavior
- MeSH Terms
-
- Animals
- Anxiety/drug therapy
- Behavior, Animal/drug effects
- Conditioning, Psychological/drug effects
- Enkephalins/genetics
- Female
- Gene Expression Regulation/drug effects
- Hydrocortisone/biosynthesis
- Hydrocortisone/metabolism
- Male
- Morphine/pharmacology*
- Protein Precursors/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Receptors, Corticotropin-Releasing Hormone/genetics
- Secologanin Tryptamine Alkaloids/pharmacology*
- Secologanin Tryptamine Alkaloids/therapeutic use
- Spatial Behavior/drug effects
- Substance Withdrawal Syndrome/drug therapy*
- Substance Withdrawal Syndrome/genetics
- Substance Withdrawal Syndrome/metabolism
- Substance Withdrawal Syndrome/psychology
- Swimming
- Zebrafish*
- PubMed
- 22205946 Full text @ PLoS One
Citation
Khor, B.S., Amar Jamil, M.F., Adenan, M.I., and Chong Shu-Chien, A. (2011) Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish. PLoS One. 6(12):e28340.
Abstract
A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping