Does prenatal methamphetamine exposure affect seizure susceptibility in adult rats with acute administration of the same drug?

Abstract

The aim of the present study was to investigate whether sensitivity to flurothyl seizures after an acute methamphetamine (MA) administration is different in prenatally MA-exposed adult rats than in controls without prenatal drug exposure. Adult male and female rats exposed prenatally to MA (5mg/kg), saline or neither (controls) were divided into groups; one group received acute MA (1mg/kg s.c.) injection and the other group received saline. Rats were then challenged with flurothyl at a constant flow rate to induce seizures. The threshold of the first focal clonus, clonic seizures and tonic-clonic seizures were analyzed. EFFECTS OF PRENATAL DRUG EXPOSURE: In animals without acute MA administration prior to seizure testing, prenatal MA exposure decreased threshold of the first clonus relative to control animals. This decrease in threshold was not apparent in groups pretreated with acute MA injection. EFFECTS OF ACUTE MA ADMINISTRATION: There was an increased threshold to both, first focal clonus and clonic seizures in animals with acute MA injection than in animals without it. The increase induced by acute MA pretreatment was higher in prenatally MA-exposed animals relative to controls. Further, clonic seizures were shorter and developed faster into tonic-clonic seizures in these acutely injected animals compared to animals without acute MA injection. EFFECTS OF HORMONES: The threshold of all measured attributes was decreased in males. Estrous cycle influences did not lead to changes between groups of prenatal exposure or acute MA administration. Threshold of tonic-clonic seizures was increased in females in proestrus/estrus stage of the estrous cycle relative to diestrous females. Our study suggests that prenatal MA exposure affects the sensitivity of adult rats to the effect of acute MA treatment prior to flurothyl seizures relative to controls.