Effect of prenatal methamphetamine exposure and challenge dose of the same drug in adulthood on epileptiform activity induced by electrical stimulation in female rats.
Our previous study demonstrated that chronic prenatal methamphetamine (MA) exposure and a single dose of MA in adulthood decrease focally induced epileptiform activity in adult male rats. As seizures are known to be dependent on sex and female estrous cycle, the goal of the present study was to examine the combined effect of prenatal MA exposure (5mg/kg) and the MA challenge dose (1mg/kg) in adulthood on electroencephalography (EEG) recordings and consequences of brain stimulation in freely moving adult female rats with respect to the estrous cycle. Overall, 12 groups of adult female rats were tested: prenatally MA-exposed, prenatally saline-exposed and rats without prenatal injections, each of these groups was either postnatally challenged with MA or with saline injection (MA-MA, MA-S; S-MA, S-S; C-MA, C-S) and further divided according to the stage of the estrous cycle to metestrus/diestrus (M/D) or proestrus/estrus (P/E). Seizures were induced by repetitive electrical stimulation (15s/8Hz) of sensorimotor cortex. Stimulation threshold, duration of afterdischarges (ADs), and presence and duration of spontaneous ADs (SADs) were evaluated. Additionally, behavior associated with stimulation and ADs, and occurrence of wet-dog-shakes (WDS) were analyzed. The present study demonstrates that the prenatal MA exposure decreased the seizure threshold in females in M/D, but not in females in P/E. In addition, prenatally MA-exposed M/D females injected with saline in adulthood had increased the duration of ADs as well as SADs. The challenge dose of MA also decreased the seizure threshold. Moreover, prenatal as well as adult MA administration decreased the number and occurrence of WDS, respectively. Thus, the present study demonstrates that the effect of prenatal MA exposure and challenge dose of the same drug on focally induced epileptiform activity in adult female rats depends on the estrous cycle.
Charles University in Prague, Third Faculty of Medicine, Department of Normal, Pathological and Clinical Physiology, Prague, Czech Republic.
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Matějovská
Charles University in Prague, Third Faculty of Medicine, Department of Normal, Pathological and Clinical Physiology, Prague, Czech Republic.
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Bernášková
Charles University in Prague, Third Faculty of Medicine, Department of Normal, Pathological and Clinical Physiology, Prague, Czech Republic. Electronic address: romana.slamberova@lf3.cuni.cz.
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Šlamberová
D000818:Animals; D000831:Animals, Newborn; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects*; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology*; D030762:Estrous Cycle; D005260:Female; D019416:Head Movements / Q000187:drug effects / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D000697:Central Nervous System Stimulants; D008694:Methamphetamine
ADs; ANOVA; EEG; GD; M/D; MA; N-Methyl-D-Aspartate; NMDA; P/E; PD; S.E.M.; SADs; WDS; afterdischarges; analysis of variance; electrical stimulation; electroencephalography; gestational day; metestrus/diestrus; methamphetamine; postnatal day; proestrus/estrus; spontaneous ADs; standard error of the mean; wet-dog-shakes