Timing of nicotine effects on learning in zebrafish

Levin, Edward D.; Limpuangthip, Joy; Rachakonda, Tara; Peterson, Miram

doi:10.1007/s00213-005-0162-9

Cited by 98 publications

(85 citation statements)

References 32 publications

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“…At present, the mechanism(s) by which atropine appears to potentiate the effects of donepezil is unclear; effects at pre-and postjunctional muscarinic receptors could be explored with the use of selective antagonists. Overall, the results obtained with donepezil in zebrafish larvae support an effect on habituation behavior via nicotinic receptors, which is in keeping with previous findings demonstrating a cognitive enhancing effect of nicotine in adult zebrafish (Levin et al, 2006a).…”

Section: Discussionsupporting

confidence: 90%

“…A number of studies in zebrafish and mammals have demonstrated learning effect through the nicotinic (Levin and Simon, 1998;Power et al, 2003;Levin et al, 2006a) and muscarinic (Levin and Simon, 1998;Power et al, 2003;Levin et al, 2006a) cholinergic receptors. 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.…”

Section: Discussionmentioning

confidence: 99%

“…These criteria become particularly demanding when it comes to modelling aspects of cognition. A number of recent studies have demonstrated the use of zebrafish as a valid subject for pharmacological modelling of behaviors and disorders seen in mammals (for review see Goldsmith, 2004), with a number of procedures using adult zebrafish having been developed for learning and memory (Williams et al, 2002;Carvan et al, 2004;Swain et al, 2004;Levin et al, 2006a). These have adapted rodent tests such as the T-maze and place preference for an aquatic environment.…”

Section: Discussionmentioning

confidence: 99%

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Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

211

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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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

211

150

View full text Add to dashboard Cite

show abstract

“…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

156

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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“…Thus far, little study has been conducted regarding the muscarinic cholinergic system, either in adult or larval zebrafish, though nicotinic receptor agonists improve spatial discrimination learning in zebrafish, which is blocked by nicotinic antagonists (Levin et al, 2006). In this study, it is hypothesized, based on the presence of choline acetyltransferase (ChAT), an acetylcholine-synthesizing enzyme, and AChE, an acetylcholine-degrading enzyme in the zebrafish brain, that the muscarinic cholinergic system plays a role in learning and memory of passive avoidance response in zebrafish.…”

Section: Introductionmentioning

confidence: 99%