Nicotinic Receptors Mediate Changes in Spinal Motoneuron Development and Axonal Pathfinding in Embryonic Zebrafish Exposed to Nicotine

Svoboda, Kurt R.; Vijayaraghavan, Sukumar; Tanguay, Robert L.

doi:10.1523/jneurosci.22-24-10731.2002

Cited by 85 publications

(87 citation statements)

References 42 publications

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“…Dlugos and Rabin (Dlugos and Rabin, 2003) and Gerlai et al (Gerlai et al, 2006) have also demonstrated adaptation of adult zebrafish after chronic exposure to ethanol such that tolerance to the acute effects of the drug develops. By contrast, studies of the effect of nicotine on zebrafish development and behaviour are limited (Levin et al, 2007;Levin and Chen, 2004;Levin et al, 2006;Matta et al, 2007;Svoboda et al, 2002). Levin et al have shown that 3·min exposure to low doses of nicotine (38-77·mol·l -1 nicotine) improves memory function in zebrafish (Levin and Chen, 2004) and that acute exposure to similar concentrations has an anxiolytic effect (Levin et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways

Kily

Cowe

Hussain

et al. 2008

Journal of Experimental Biology

158

123

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SUMMARYAddiction is a complex psychiatric disorder considered to be a disease of the brain's natural reward reinforcement system. Repeated stimulation of the 'reward' pathway leads to adaptive changes in gene expression and synaptic organization that reinforce drug taking and underlie long-term changes in behaviour. The primitive nature of reward reinforcement pathways and the near universal ability of abused drugs to target the same system allow drug-associated reward and reinforcement to be studied in non-mammalian species. Zebrafish have proved to be a valuable model system for the study of vertebrate development and disease. Here we demonstrate that adult zebrafish show a dose-dependent acute conditioned place preference (CPP) reinforcement response to ethanol or nicotine. Repeated exposure of adult zebrafish to either nicotine or ethanol leads to a robust CPP response that persists following 3·weeks of abstinence and in the face of adverse stimuli, a behavioural indicator of the establishment of dependence. Microarray analysis using whole brain samples from drug-treated and control zebrafish identified 1362 genes that show a significant change in expression between control and treated individuals. Of these genes, 153 are common to both ethanol-and nicotine-treated animals. These genes include members of pathways and processes implicated in drug dependence in mammalian models, revealing conservation of neuro-adaptation pathways between zebrafish and mammals.Supplementary material available online at

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Section: Discussionmentioning

confidence: 99%

Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways

Kily

Cowe

Hussain

et al. 2008

Journal of Experimental Biology

158

123

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“…Levin and Chen (2004) and Levin et al (2006b) have studied extensively the effects of nicotine on learning and memory in zebrafish and have shown that low doses of nicotine enhance memory while higher doses impair memory in zebrafish. Zebrafish larvae possess acetylcholinesterase with similar enzymatic activity to other vertebrates, but do not have butyrylcholinesterase (Svoboda et al, 2002), and cloning and binding experiments have demonstrated the presence of nicotinic (b3, a2, and a7 subunits) (Zirger et al, 2003) and muscarinic receptors (Williams and Messer, 2004) in zebrafish embryo. To determine whether the enhanced startle response observed with the cholinesterase inhibitor donepezil was mediated via either nicotinic or muscarinic receptors or both types of receptors, donepezil treatment was combined with the nicotinic antagonist mecamylamine or the muscarinic antagonist atropine.…”

Section: Discussionmentioning

confidence: 99%

Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

216

150

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Habituation, where a response is reduced when exposed to a continuous stimulus is one of the simplest forms of non-associative learning and has been shown in a number of organisms from sea slugs to rodents. However, very little has been reported in the zebrafish, a model that is gaining popularity for high-throughput compound screens. Furthermore, since most of the studies involving learning and memory in zebrafish have been conducted in adults, we sought to determine if zebrafish larvae could display non-associative learning and whether it could be modulated by compounds identified in previous rodent studies. We demonstrated that zebrafish larvae (7 days post fertilization) exhibit iterative reduction in a startle response to a series of acoustic stimuli. Furthermore, this reduction satisfied criteria for habituation: spontaneous recovery, more rapid reductions in startle to shorter intertrial intervals and dishabituation. We then investigated the pathways mediating this behavior using established compounds in learning and memory. Administration of rolipram (PDE4 inhibitor), donepezil (acetylcholinesterase inhibitor), and memantine (N-methyl-D-aspartic acid (NMDA) receptor antagonist) all increased the acoustic startle response and decreased habituation in the larvae, similar to previous rodent studies. Further studies demonstrated that NMDA blocked the memantine response and the effect of donepezil was blocked by mecamylamine but not atropine suggesting that the donepezil response was mediated by nicotinic rather than muscarinic receptors. Zebrafish larvae possess numerous advantages for medium to high-throughput screening; the model described herein therefore offers the potential to screen for additional compounds for further study on cognition function.

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“…A pioneering study of nicotine effects on neural development demonstrated that exposure early in embryonic development induced axons path-finding errors (Svoboda, Vijayaraghavan, & Tanguay, 2002). Zebrafish were exposed to 5, 15, and 33 mM nicotine, with 33 mM selected for most experiments because it elicited the strongest alteration in embryonic zebrafish behavior.…”

Section: Embryonic Developmentmentioning

confidence: 99%

Zebrafish for the Study of the Biological Effects of Nicotine

Klee

Ebbert

Schneider

et al. 2011

Nicotine & Tobacco Research

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Introduction: Zebrafish are emerging as a powerful animal model for studying the molecular and physiological effects of nicotine exposure. The zebrafish have many advantageous physical characteristics, including small size, high fecundity rates, and externally developing transparent embryos. When combined with a battery of molecular-genetic tools and behavioral assays, these attributes enable studies to be conducted that are not practical using traditional animal models. Methods:We reviewed the literature on the application of the zebrafish model as a preclinical model to study the biological effects of nicotine exposure. Results:The identified studies used zebrafish to examine the effects of nicotine exposure on early development, addiction, anxiety, and learning. The methods used included green fluorescent protein-labeled proteins to track in vivo nicotine-altered neuron development, nicotine-conditioned place preference, and locomotive sensitization linked with high-throughput molecular and genetic screens and behavioral models of learning and stress response to nicotine. Data are presented on the complete homology of all known human neural nicotinic acetylcholine receptors in zebrafish and on the biological similarity of human and zebrafish dopaminergic signaling.Conclusions: Tobacco dependence remains a major health problem worldwide. Further understanding of the molecular effects of nicotine exposure and genetic contributions to dependence may lead to improvement in patient treatment strategies. While there are limitations to the use of zebrafish as a preclinical model, it should provide a valuable tool to complement existing model systems. The reviewed studies demonstrate the enormous opportunity zebrafish have to advance the science of nicotine and tobacco research.

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Nicotinic Receptors Mediate Changes in Spinal Motoneuron Development and Axonal Pathfinding in Embryonic Zebrafish Exposed to Nicotine

Cited by 85 publications

References 42 publications

Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways

Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways

Non-Associative Learning in Larval Zebrafish

Zebrafish for the Study of the Biological Effects of Nicotine

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