Abstract
Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory γ-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play an important role in the effect of stimulants on epileptic seizures. No studies investigating the effect of prenatal methamphetamine (MA) exposure on seizures are available. In this study, bicuculline (GABAA receptor antagonist), NMDA (NMDA receptor agonist) and kainic acid (non-NMDA receptor agonist) were used to induce seizures in adult male rats. Three groups of animals were tested in each seizure test: prenatally MA- (5 mg/kg) exposed, prenatally saline-exposed, and absolute controls without any prenatal exposure. In bicuculline-induced seizures, the latency to onset of tonic–clonic seizures was shorter in MA-exposed rats than in controls, but it did not differ from saline-exposed rats. There were no differences in clonic seizure onset between groups. In NMDA-induced seizures, the latency to onset of clonic–tonic seizures was shorter in prenatally MA-exposed rats than in controls; however, the latency to onset of saline-exposed animals did not differ from either MA-exposed or from control rats. There were no differences in seizure susceptibility in kainic acid-induced clonic seizures. There were no differences in seizure incidences or stereotypical behavior in any seizure model. The question remains as to how much the present data demonstrate the effect of prenatal drug exposure on seizure susceptibility per se, and how much they may be explained by the effect of prenatal stress or by other mechanism(s).
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Acknowledgements
This study was supported by grants # 305/03/0774 from the Grant Agency of the Czech Republic and # 1A8610–5/2005 from the Internal Grant Agency of the Ministry of Health of the Czech Republic to R.Š., and by Research Goal # MSM 0021620816 from the Ministry of Education, Youth and Sports of the Czech Republic to R.R. The authors express their appreciation to Dr. Ilona Vathy for critical reading and editing of the manuscript. The procedures for animal experimentation utilized in this report were reviewed and approved by the Institutional Animal Care and Use Committee and are in agreement with the Principles of Laboratory Animal Care (NIH publication No. 85–23, revised 1985).
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Šlamberová, R., Rokyta, R. Occurrence of bicuculline-, NMDA- and kainic acid-induced seizures in prenatally methamphetamine-exposed adult male rats. Naunyn Schmied Arch Pharmacol 372, 236–241 (2005). https://doi.org/10.1007/s00210-005-0016-3
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DOI: https://doi.org/10.1007/s00210-005-0016-3