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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.

Anticholinergic drugs based on tropane alkaloids, including atropine, scopolamine, and hyoscyamine, have been used for various medicinal and toxic purposes for millennia. These drugs are competitive antagonists of acetylcholine muscarinic (M-) receptors that potently modulate the central nervous system (CNS). Currently used clinically to treat vomiting, nausea, and bradycardia, as well as alongside other anesthetics to avoid vagal inhibition, these drugs also evoke potent psychotropic effects, including characteristic delirium-like states with hallucinations, altered mood, and cognitive deficits. Given the growing clinical importance of anti-M deliriant hallucinogens, here we discuss their use and abuse, clinical importance, and the growing value in preclinical (experimental) animal models relevant to modeling CNS functions and dysfunctions.

Currently becoming widely recognized, personalized psychiatry focuses on unique physiological and genetic profiles of patients to best tailor their therapy. However, the role of individual differences, as well as genetic and environmental factors, in human psychiatric disorders remains poorly understood. Animal experimental models are a valuable tool to improve our understanding of disease pathophysiology and its molecular mechanisms. Due to high reproduction capability, fully sequenced genome, easy gene editing, and high genetic and physiological homology with humans, zebrafish (Danio rerio) are emerging as a novel powerful model in biomedicine.Mounting evidence supports zebrafish as a useful model organism in CNS research.Robustly expressed in these fish, individual, strain, and sex differences shape their CNS responses to genetic, environmental, and pharmacological manipulations. Here, we discuss zebrafish as a promising complementary translational tool to further advance patient-centered personalized psychiatry. K E Y W O R D Sgene-environment interactions, individual differences, personalized psychiatry, zebrafish | 403 VOLGIN et aL.

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