Nicotinic Antagonist UFR2709 Inhibits Nicotine Reward and Decreases Anxiety in Zebrafish

Viscarra, Franco; González-Gutiérrez, Juan Pablo; Esparza, Erica; Figueroa, Carla; Paillali, Pablo; Hödar-Salazar, Martín; Céspedes, Camilo; Quiroz, Gabriel; Sotomayor‐Zárate, Ramón; Reyes‐Parada, Miguel; Bermúdez, Isabel; Iturriaga-Vásquez, Patricio

doi:10.3390/molecules25132998

Cited by 8 publications

(12 citation statements)

References 46 publications

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“…This behavioral paradigm has been previously validated by many labs to test the anxiolytic-like effects of compounds, such as nicotine, fluoxetine, diazepam, buspirone, chlordiazepoxide, and tranylcypromine [ 5 , 6 , 10 , 14 , 18 , 22 , 25 , 26 , 29 , 30 , 32 , 36 , 37 , 39 , 44 , 50 , 53 , 57 – 59 , 66 ]. In fact, regulation of this anxiety-like behavior by nicotine and other nicotinic ligands has been reported in several publications, supporting the pharmacological relevance of nAChR in zebrafish anxiety [ 5 , 28 , 32 , 33 , 53 , 67 ].…”

Section: Introductionsupporting

confidence: 52%

“…Many publications now support the suitability of zebrafish to model various aspects of anxiety-related states [ 26 , 30 , 58 ]. In fact, zebrafish NTT has been validated using several clinical anxiolytic compounds, including buspirone, fluoxetine, diazepam, chlordiazepoxide, and tranylcypromine [ 5 , 6 , 10 , 14 , 18 , 22 , 25 , 26 , 29 , 30 , 32 , 36 , 37 , 39 , 44 , 50 , 53 , 57 – 59 , 66 ] and has also shown to be sensitive to nicotine and other nicotinic ligands [ 5 , 28 , 32 , 33 , 53 , 67 ]. In this study, we investigated the effects of nicotine and six additional nAChR-activating alkaloids on the NTT.…”

Section: Discussionmentioning

confidence: 99%

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Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish

Alzualde¹,

Jaka²,

Latino

et al. 2021

J Nat Med

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Alkaloids are a structurally complex group of natural products that have a diverse range of biological activities and significant therapeutic applications. In this study, we examined the acute, anxiolytic-like effects of nicotinic acetylcholine receptor (nAChR)-activating alkaloids with reported neuropharmacological effects but whose effects on anxiety are less well understood. Because α4β2 nAChRs can regulate anxiety, we first demonstrated the functional activities of alkaloids on these receptors in vitro. Their effects on anxiety-like behavior in zebrafish were then examined using the zebrafish novel tank test (NTT). The NTT is a relatively high-throughput behavioral paradigm that takes advantage of the natural tendency of fish to dive down when stressed or anxious. We report for the first time that cotinine, anatabine, and methylanatabine may suppress this anxiety-driven zebrafish behavior after a single 20-min treatment. Effective concentrations of these alkaloids were well above the concentrations naturally found in plants and the concentrations needed to induce anxiolytic-like effect by nicotine. These alkaloids showed good receptor interactions at the α4β2 nAChR agonist site as demonstrated by in vitro binding and in silico docking model, although somewhat weaker than that for nicotine. Minimal or no significant effect of other compounds may have been due to low bioavailability of these compounds in the brain, which is supported by the in silico prediction of blood–brain barrier permeability. Taken together, our findings indicate that nicotine, although not risk-free, is the most potent anxiolytic-like alkaloid tested in this study, and other natural alkaloids may regulate anxiety as well.

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Section: Introductionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish

Alzualde¹,

Jaka²,

Latino

et al. 2021

J Nat Med

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“…A study by Viscarra F et al, reported there was no big difference in β-actin expression among the control and the stressed fish. Using standard RT-PCR, the level of mRNA expression of α4 nACh and α7 nACh receptor subunits in the brain of adult zebrafish exposed with net stressor was determined and found the level of expression of α4 and α7 receptor subunit of mRNA were significantly reduce [87]. Cytokines are important brain mediators in neuromodulation, and they are especially useful for investigating modelling psychological effects [88,89].…”

Section: Gene Expressionmentioning

confidence: 99%

Zebrafish as an Emerging Alternative Tool for Studying Anxiety Disorders

War

Surendra

Paul

et al. 2022

JASR

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Zebrafish are increasingly becoming popular as promising new model species for translational research in a variety of neurological fields. Because of their complex behaviors across all major neurobehavioral domains and strong genetic and physiological similarities to humans, zebrafish are well-suited to modelling many aspects of anxiety-related states. In this paper, we first summarized the behavioral models available in zebrafish, such as novel tank test, light/dark box test, open field test, and social preference test, and their efficacy in discovering anxiety-like indices in zebrafish, followed by highlighting the key neurotransmitter systems, such as glutamate and GABA. In addition, cortisol levels and gene expression were explored as well. Overall, this review discusses the benefits of using the zebrafish model for anxiety research and examines current research in the field.

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“…The α4β2 subtypes, which are the major nAChRs present in the central nervous system (CNS) [ 6 , 7 ] have been proposed as the principal subtypes involved in anxiety and nicotine addiction; however, another nAChR subtype could contribute to these disorders. The nAChR subtypes have been studied in different animal models such as non-human primates, cats, frogs, rats, mice, and zebrafish, associated with different behaviors such as memory loss and drug abuse, among others, and play a key role in the anxiolytic activity of nicotine [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Its versatility in development and the number of individuals for experimentation make the zebrafish an appropriate animal model for studying new drugs [ 20 , 21 ]. Behavioral studies have been used with zebrafish in complex paradigms related to memory, anxiety, stress, addiction, and the reinforcing properties of drug abuse [ 11 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Behavioral Study of 3- and 5-Halocytisine Derivatives in Zebrafish Using the Novel Tank Diving Test (NTT)

Farías-Cea,

Leal,

Hödar-Salazar

et al. 2023

IJMS

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Anxiety is a serious mental disorder, and recent statistics have determined that 35.12% of the global population had an anxiety disorder during the COVID-19 pandemic. A mechanism associated with anxiolytic effects is related to nicotinic acetylcholine receptor (nAChR) agonists, principally acting on the α4β2 nAChR subtype. nAChRs are present in different animal models, including murine and teleosteos ones. Zebrafish has become an ideal animal model due to its high human genetic similarities (70%), giving it high versatility in different areas of study, among them in behavioral studies related to anxiety. The novel tank diving test (NTT) is one of the many paradigms used for studies on new drugs related to their anxiolytic effect. In this work, an adult zebrafish was used to determine the behavioral effects of 3- and 5-halocytisine derivatives, using the NTT at different doses. Our results show that substitution at position 3 by chlorine or bromine decreases the time spent by the fish at the bottom compared to the control. However, the 3-chloro derivative at higher doses increases the bottom dwelling time. In contrast, substitution at the 5 position increases bottom dwelling at all concentrations showing no anxiolytic effects in this model. Unexpected results were observed with the 5-chlorocytisine derivative, which at a concentration of 10 mg/L produced a significant decrease in bottom dwelling and showed high times of freezing. In conclusion, the 3-chloro and 3-bromo derivatives show an anxiolytic effect, the 3-chlorocytisine derivative being more potent than the 3-bromo derivative, with the lowest time at the bottom of the tank at 1mg/L. On the other hand, chlorine, and bromine at position 5 produce an opposite effect.

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Nicotinic Antagonist UFR2709 Inhibits Nicotine Reward and Decreases Anxiety in Zebrafish

Cited by 8 publications

References 46 publications

Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish

Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish

Zebrafish as an Emerging Alternative Tool for Studying Anxiety Disorders

Behavioral Study of 3- and 5-Halocytisine Derivatives in Zebrafish Using the Novel Tank Diving Test (NTT)

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