Time-dependent interacting effects of caffeine, diazepam, and ethanol on zebrafish behaviour

Tran, Steven; Fulcher, Niveen; Nowicki, Magda; Desai, Priyanka; Tsang, Benjamin; Facciol, Amanda; Chow, Hayden; Gerlai, Robert

doi:10.1016/j.pnpbp.2016.12.004

Cited by 46 publications

(41 citation statements)

References 54 publications

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“…Ethanol (alcohol or ethyl alcohol) is one of the most widely abused drugs consumed in the world [ 5 ] and therefore its toxic and psychoactive effect has been thoroughly studied. Zebrafish ( Danio rerio ) has been proposed as an ideal vertebrate model to investigate the neurobehavioural effects of ethanol addiction [ 6 ] as well as the mechanisms underlying those effects [ 7 – 9 ] mostly because ethanol metabolism in zebrafish liver is similar to humans [ 10 ]. In addition, zebrafish can be easily kept and bred in the laboratory, providing readily access at the embryonic and larval stages for genetic and screening tests [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Ethanol toxicity differs depending on the time of day

et al. 2018

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Ethanol is one of the most commonly abused drugs and consequently its toxic and psychoactive effect has been widely investigated, although little is known about the time-dependent effects of this drug. In the present research zebrafish was used to assess daily rhythms in ethanol toxicity and behavioural effects, as well as the temporal pattern of expression of key genes involved in ethanol detoxification in the liver (adh8a, adh5, aldh2.1 and aldh2.2). Our results showed marked differences in the mortality rate of zebrafish larvae depending on the time of day of the exposure to 5% ethanol for 1h (82% and 6% mortality in the morning and at night, respectively). A significant daily rhythm was detected with the acrophase located at “zeitgeber” time (ZT) = 04:22 h. Behavioural tests exposing zebrafish to 1% ethanol provoked a major decrease in swimming activity (68–84.2% reduction) at ZT2, ZT6 and ZT10. In contrast, exposure at ZT18 stimulated swimming activity (27% increase). During the day fish moved towards the bottom of the tank during ethanol exposure, whereas at night zebrafish increased their activity levels right after the exposure to ethanol. Genes involved in ethanol detoxification failed to show significant daily rhythms in LD, although all of them exhibited circadian regulation in constant darkness (DD) with acrophases in phase and located at the end of the subjective night. Taken altogether, this research revealed the importance of considering the time of day when designing and carrying out toxicological and behavioural tests to investigate the effects of ethanol, as the adverse effects of this drug were more marked when fish were exposed in the morning than at night.

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Section: Introductionmentioning

confidence: 99%

Ethanol toxicity differs depending on the time of day

et al. 2018

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“…This absence of an effect on of Glo1 manipulations on ethanol locomotor response, especially ethanol locomotor sedation, is surprising given the considerable literature showing that other GABAergic drugs act synergistically with ethanol to potentiate sedative effects (e.g. Tran et al, 2017;Vanover et al, 1999;Saeed Dar, 2006;Holstein et al, 2009;Dudek & Phillips, 1989).…”

Section: Discussionmentioning

confidence: 97%

“…Specifically, it has been well-established that enhanced locomotor sedation and ataxia is observed when ethanol and GABAergic agonists or positive modulators are co-administered (e.g. Tran et al, 2017;Vanover et al, 1999;Saeed Dar, 2006;Holstein et al, 2009;Dudek & Phillips, 1989). Additive locomotor effects with ethanol could potentially explain a compound's ability to reduce ethanol consumption due to an increase in competing behaviors (e.g.…”

Section: Introductionmentioning

confidence: 99%

Glyoxalase (GLO1) inhibition or genetic overexpression does not alter ethanol’s locomotor effects: implications for GLO1 as a therapeutic target in alcohol use disorders

Barkley-Levenson

Lagarda

Palmer

2017

Preprint

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Background: Glyoxalase 1 (GLO1) is an enzyme that metabolizes the glycolytic byproduct methylglyoxal (MG), which is a competitive partial agonist at GABAA receptors.Pharmacological inhibition of GLO1 increases concentrations of MG in the brain and decreases binge-like ethanol drinking. The present study assessed whether pharmacological inhibition of GLO1, or genetic over expression of Glo1, would also alter the locomotor effects of ethanol, which might explain reduced ethanol consumption following GLO1 inhibition. We used the prototypical GABAA receptor agonist muscimol as a positive control.Methods: Male C57BL/6J mice were pretreated with a single dose of either the GLO1 inhibitor S-bromobenzylglutathione cyclopentyl diester (pBBG; 7.5 mg/kg; Experiment 1) or muscimol (0.75 mg/kg; Experiment 2), or their corresponding vehicle. We then determined whether the locomotor response to a range of ethanol doses (0, 0.5, 1.0, 1.5, 2.0, and 2.5) was altered by either pBBG or muscimol pretreatment. We also examined the locomotor response to a range of ethanol doses in FVB/NJ wild type and transgenic Glo1 over expressing mice (Experiment 3).We also assessed anxiety-like behavior as measured by time spent in the center of an open field in all three experiments. Results:The ethanol dose-response curve was not altered by pretreatment with pBBG or by transgenic overexpression of Glo1. In contrast, muscimol blunted locomotor stimulation at low ethanol doses, and potentiated locomotor sedation at higher ethanol doses. Conclusions:The dose of pBBG used in this study has been previously shown to reduce ethanol drinking. Glo1 overexpression has been previously shown to increase ethanol drinking.However, neither manipulation altered the dose response curve for ethanol's locomotor effects, whereas muscimol appeared to enhance the locomotor sedative effects of ethanol. The present ! 2 data demonstrate that reduced ethanol drinking caused by GLO1 inhibition is not due to potentiation of ethanol's stimulant or depressant effects.

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“…However, the similar pattern of results between Experiments 1 and 3 (i.e., no effect of GLO1 inhibitor treatment or genetic overexpression of Glo1 ) does suggest that these findings generalize across genotypes. This absence of an effect of GLO1 manipulations on EtOH locomotor response, especially EtOH locomotor sedation, is surprising given the considerable literature showing that other GABAergic drugs act synergistically with EtOH to potentiate sedative effects (e.g., Dudek and Phillips, ; Holstein et al., ; Saeed Dar, ; Tran et al., ; Vanover et al., ).…”

Section: Discussionmentioning

confidence: 98%

“…Substantial previous work with various GABAergic agonists and positive allosteric modulators indicates that compounds that increase GABAergic activity can produce additive effects when administered with EtOH. Specifically, it has been well‐established that enhanced locomotor sedation and ataxia are observed when EtOH and GABAergic agonists or positive modulators are co‐administered (e.g., Dudek and Phillips, ; Holstein et al., ; Saeed Dar, ; Tran et al., ; Vanover et al., ). Additive locomotor effects with EtOH could potentially explain a compound's ability to reduce EtOH consumption due to an increase in competing behaviors (e.g., locomotor activation) or through increased sedative effects that limit consumption.…”

mentioning

confidence: 99%

Glyoxalase 1 (GLO1) Inhibition or Genetic Overexpression Does Not Alter Ethanol's Locomotor Effects: Implications for GLO1 as a Therapeutic Target in Alcohol Use Disorders

Barkley-Levenson

Lagarda

Palmer

2018

Alcoholism Clin & Exp Res

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The dose of pBBG used in this study is within the effective range shown previously to reduce EtOH drinking. Glo1 overexpression has been previously shown to increase EtOH drinking. However, neither manipulation altered the dose-response curve for EtOH's locomotor effects, whereas muscimol appeared to enhance the locomotor sedative effects of EtOH. The present data demonstrate that reduced EtOH drinking caused by GLO1 inhibition is not due to potentiation of EtOH's stimulant or depressant effects.

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Time-dependent interacting effects of caffeine, diazepam, and ethanol on zebrafish behaviour

Cited by 46 publications

References 54 publications

Ethanol toxicity differs depending on the time of day

Ethanol toxicity differs depending on the time of day

Glyoxalase (GLO1) inhibition or genetic overexpression does not alter ethanol’s locomotor effects: implications for GLO1 as a therapeutic target in alcohol use disorders

Glyoxalase 1 (GLO1) Inhibition or Genetic Overexpression Does Not Alter Ethanol's Locomotor Effects: Implications for GLO1 as a Therapeutic Target in Alcohol Use Disorders

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