Assessment of the convulsant liability of antidepressants using zebrafish and mouse seizure models

Vermoesen, Katia; Serruys, Ann-Sophie K.; Loyens, Ellen; Afrikanova, Tatiana; Massie, Ann; Schallier, Anneleen; Michotte, Yvette; Crawford, Alexander D.; Esguerra, Camila V.; Witte, Peter de; Smolders, Ilse Julia; Clinckers, Ralph

doi:10.1016/j.yebeh.2011.08.016

Cited by 41 publications

(28 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rodent models, the latency to clonic seizure-like behavior is used in screening studies of new AED discovery [41], [42]. However, our results indicate that the analyses of several parameters, rather than only one, could provide a better and reliable instrument that could be used for screening new drugs.…”

Section: Discussionmentioning

confidence: 91%

Seizures Induced by Pentylenetetrazole in the Adult Zebrafish: A Detailed Behavioral Characterization

et al. 2013

View full text Add to dashboard Cite

Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.

show abstract

Section: Discussionmentioning

confidence: 91%

Seizures Induced by Pentylenetetrazole in the Adult Zebrafish: A Detailed Behavioral Characterization

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Numerous studies have showed that adult or zebra-fish larvae exposed to PTZ exhibit increased locomotor activity, seizure-like behavior, and epileptiform electrographic activity [15,19] [ [22][23][24], which have a good correlation between zebra-fish and rodent data [15,17,21,25]. Also, many researchers have used zebra-fish seizure model for anti- convulsions in zebra-fish larvae was assessed through quantification of the high-speed moved distance.…”

Section: Discussionmentioning

confidence: 99%

Validation of the Zebra-fish Pentylene Tetrazol Seizure Model: Behaviour Assay for Assessing Anti-Epileptic Drug Efficacy

Liu¹,

Zhou²

2016

Biochem Anal Biochem

View full text Add to dashboard Cite

The availability of zebra-fish larvae model of epileptic seizure provides opportunities to identify novel anticonvulsants for treatment of people with epilepsy. However, the major parameters of zebra-fish behavior assay for assessing antiepileptic drug efficacy existed disparity, which resulted in different results in previous studies. In this study, we chose the high, medium, slow-speed moved distances and the total distances moved for seizure-like activity quantification in individual wells of a 48-well plate in the dark phase and used this zebra-fish seizure model to assess three commonly prescribed anti-epileptic drug's efficacy and screen bioactive components from plant extract. Results showed that the high-speed moved distances were given a more reasonable and sensitive dose-response curve than the total distances in zebra-fish larvae model exposed to 10 mM pentylene tetrazole. Besides, we also optimized the vehicle (dimethyl sulfoxide, DMSO) concentration used in epileptic behaviour assay. The three anti-epileptic drugs, phenytoin, valproate sodium and carbamazepine showed the same efficacy patterns in zebra-fish seizure model as in mammalian epileptic models. We also found four positive hits from plant (Vaccinium spp.) extract in primary drug screening, two hits exhibited concentration-dependent inhibition of locomotor activity, confirming their anticonvulsant characteristics. These results indicated that this zebra-fish larvae model could be useful for assessing anti-epileptic drug efficacy, facilitating the primary drug screening and evaluating of effective components in medicinal plants.

show abstract

“…Chronic administration of bupropione at doses of 7.5-10 mg/kg twice daily significantly raised the electroconvulsive threshold in mice [101]. Bupropion failed to affect PTZ-, kainic acid-and flurothyl-induced seizures in mice, but reduced the convulsive-like behaviour in the zebrafish larva PTZ model and facilitated limbic seizures induced by pilocarpine in mice [64,96,99].…”

Section: Reboxetinementioning

confidence: 92%

“…In mice, the antidepressant (10-20 mg/kg) increased the PTZ seizure threshold, whereas at the dose of 30 mg/kg it facilitated pilocarpine-induced limbic seizures [96].…”

Section: Reboxetinementioning

confidence: 94%

“…Reboxetine at doses of 20-30 mg/kg decreased seizure activity in the kainic acidinduced post status epilepticus rat model for temporal lobe epilepsy [95], zebrafish larva PTZ model, but not in pilocarpine-induced seizures [96]. In mice, the antidepressant (10-20 mg/kg) increased the PTZ seizure threshold, whereas at the dose of 30 mg/kg it facilitated pilocarpine-induced limbic seizures [96].…”

Section: Reboxetinementioning

confidence: 96%

See 1 more Smart Citation

Pharmacokinetic/pharmacodynamic considerations for epilepsy – depression comorbidities

Banach

Popławska

Błaszczyk³

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

The preclinical data may provide valuable clues on how to combine these two groups of drugs - antidepressant drugs neutral or potentiating the anticonvulsant action of antiepileptics are recommended in this regard. Avoidance of antidepressants clearly decreasing the convulsive threshold or decreasing the anticonvulsant efficacy of antiepileptic drugs (f.e. bupropion or mianserin) in patients with epilepsy is recommended.

show abstract

Assessment of the convulsant liability of antidepressants using zebrafish and mouse seizure models

Cited by 41 publications

References 56 publications

Seizures Induced by Pentylenetetrazole in the Adult Zebrafish: A Detailed Behavioral Characterization

Seizures Induced by Pentylenetetrazole in the Adult Zebrafish: A Detailed Behavioral Characterization

Validation of the Zebra-fish Pentylene Tetrazol Seizure Model: Behaviour Assay for Assessing Anti-Epileptic Drug Efficacy

Pharmacokinetic/pharmacodynamic considerations for epilepsy – depression comorbidities

Contact Info

Product

Resources

About