PUBLICATION
Evidence of an antidepressant-like effect of xylopic acid mediated by serotonergic mechanisms
- Authors
- Biney, R.P., Benneh, C.K., Adongo, D.W., Ameyaw, E.O., Woode, E.
- ID
- ZDB-PUB-210411-4
- Date
- 2021
- Source
- Psychopharmacology 238(8): 2105-2120 (Journal)
- Registered Authors
- Keywords
- 5-Hydroxytryptamine, Glutamate, Major depressive disorder, Neuroprotection, Zebrafish
- MeSH Terms
-
- Animals
- Antidepressive Agents/pharmacology
- Antidepressive Agents/therapeutic use*
- Brain/drug effects*
- Brain/metabolism*
- Depression/drug therapy*
- Depression/metabolism
- Depression/psychology
- Diterpenes, Kaurane/pharmacology
- Diterpenes, Kaurane/therapeutic use*
- Dose-Response Relationship, Drug
- Hindlimb Suspension/adverse effects
- Hindlimb Suspension/psychology
- Male
- Mice
- Mice, Inbred ICR
- Monoamine Oxidase/metabolism
- Monoamine Oxidase Inhibitors/pharmacology
- Organ Culture Techniques
- Rats
- Rats, Sprague-Dawley
- Serotonin/metabolism*
- Serotonin Antagonists/pharmacology
- Serotonin Antagonists/therapeutic use
- Swimming/psychology
- Zebrafish
- PubMed
- 33837810 Full text @ Psychpharma
Citation
Biney, R.P., Benneh, C.K., Adongo, D.W., Ameyaw, E.O., Woode, E. (2021) Evidence of an antidepressant-like effect of xylopic acid mediated by serotonergic mechanisms. Psychopharmacology. 238(8):2105-2120.
Abstract
Background Depression causes significant debilitating symptoms and economic burden. Current management is challenged by slow onset of action and modest efficacies of antidepressants; thus, the search for newer antidepressants remains relevant. We evaluated the antidepressant effects of a kaurene diterpene, xylopic acid (XA), in zebrafish and mouse models.
Methods The chronic unpredictable stress (CUS) protocol in zebrafish and the tail suspension test (TST), forced swim test (FST), lipopolysaccharide-induced depression-like behaviour test (LID) and repeated open space swimming test (OSST) in mice were used. We further examined the impact of depleting monoamines on XA's antidepressant effects. The contribution of glutamatergic and nitrergic pathways on the antidepressant effect of XA in mice and XA's effects on 5-HT receptors and monoamine oxidase (MAO) enzymes were also evaluated. Finally, XA's influence on neuroprotection was evaluated by measuring BDNF and oxidative stress enzymes in whole brain. XA doses (1-10 μM) in zebrafish and (10, 30, 100 mg kg-1) in mice exerted potent antidepressant-like potential in FST, TST, LID and showed fast-onset antidepressant-like property in the OSST.
Results The antidepressant-like properties in mice were reversed by blocking synthesis/release of serotonin but not noradrenaline using p-chlorophenylalanine and α-methyl-p-tyrosine, respectively. This antidepressant-like effect was potentiated by D-cycloserine and Nω-Nitro-L-arginine methyl ester (L-NAME) but not by D-serine and L-arginine. XA also evoked partial agonist-like effects on 5-hydroxytrptamine receptors on the rat fundus but it did not have MAO inhibition effect. It also increased BDNF, glutathione and antioxidant enzymes.
Conclusion Therefore, xylopic acid possesses antidepressant-like effects largely mediated by serotonergic and neuroprotective mechanisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping