Dongmei Wang

Bio: Dongmei Wang is an academic researcher from Southwest University. The author has contributed to research in topics: Zebrafish & Kava. The author has an hindex of 7, co-authored 13 publications receiving 107 citations.

DARK Classics in Chemical Neuroscience: Arecoline.

Abstract: Arecoline is a naturally occurring psychoactive alkaloid from areca (betel) nuts of the areca palm ( Areca catechu) endemic to South and Southeast Asia. A partial agonist of nicotinic and muscarinic acetylcholine receptors, arecoline evokes multiple effects on the central nervous system (CNS), including stimulation, alertness, elation, and anxiolysis. Like nicotine, arecoline also evokes addiction and withdrawal symptoms (upon discontinuation). The abuse of areca nuts is widespread, with over 600 million users globally. The importance of arecoline is further supported by its being the world's fourth most commonly used human psychoactive substance (after alcohol, nicotine, and caffeine). Here, we discuss neuropharmacology, pharmacokinetics, and metabolism of arecoline, as well as social and historical aspects of its use and abuse. Paralleling clinical findings, we also evaluate its effects in animal models and outline future clinical and preclinical CNS research in this field.

Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia

Abstract: Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation.

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression.

Abstract: Depression is one of the global leading causes of disability, but treatments remain limited and classical antidepressants were found to be ineffective in a substantial proportion of patients. Thus, novel effective therapies for the treatment of depression are urgently needed. Given the emerging role of inflammation in the etiology and pathophysiology of affective disorders, we herein illustrate how experimental endotoxemia, a translational model of systemic inflammation, could be used as a tool to develop and test new therapeutic options against depression. Our concept is based on the striking overlap of inflammatory, neural, and affective characteristics in patients with inflammation-associated depression and in endotoxin-challenged healthy subjects. Experimental administration of endotoxin in healthy volunteers is safe, well-tolerated, and without known long-term health risks. It offers a highly standardized translational approach to characterize potential targets of therapies against inflammation-associated depression, as well as to identify characteristics of patients that would benefit from these interventions, and, therefore, could contribute to improve personalization of treatment and to increase the overall rate of responders.

Sex differences in behavior and neuropharmacology of zebrafish.

Abstract: Sex is an important variable in biomedical research. The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in translational neuroscience and pharmacology. Mounting evidence indicates important sex differences in zebrafish behavioral and neuropharmacological responses. Here, we discuss the role of sex in zebrafish central nervous system (CNS) models, their molecular mechanisms, recent findings and the existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of sex differences, fostering future CNS drug discovery and the search for novel sex-specific therapies. Finally, we highlight the interplay between sex and environment in zebrafish models of sex-environment correlations as an important strategy of CNS disease modeling using this aquatic organism.

Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia

Abstract: Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation.