Exogenous antenatal glucocorticoid treatment reduces susceptibility for hippocampal kindled and maximal electroconvulsive seizures in infant rats.
Dexamethasone (DEX) and betamethasone (BETA) are synthetic glucocorticoids used clinically to reduce morbidity and mortality in infants at risk of premature birth. While their main role is to facilitate lung development, their effect on the developing nervous system and seizure susceptibility is unclear. The present study tested the hypothesis that antenatal DEX or BETA treatment would alter seizure thresholds and spread of epileptiform activity in the brains of infant offspring. Pregnant dams received once daily injections with DEX, BETA, or vehicle on gestation days 15 to 18. Physical appearance, litter size, and weight of the pups were assessed postnatally. Seizure thresholds were determined on postnatal day 14 using electroconvulsive shock delivered through ear clips (i.e., generalized seizure) or kindling stimulation of the left hippocampus through indwelling electrodes (i.e., partial seizure). The rate of acquisition of kindled seizures was determined on postnatal days 14 and 15. Pups from dams treated with DEX and BETA were growth restricted. Antenatal BETA treatment increased seizure threshold for both models. Antenatal DEX treatment increased kindling threshold, but not electroconvulsive shock threshold. Kindling rate was unaffected by either antenatal treatment. In summary, repeated glucocorticoid treatments had adverse effects on weight, skin and litter size, raised seizure thresholds, and reduced seizure vulnerability. Although these effects are seemingly desirable with respect to seizure susceptibility, they suggest that the functional organization of the nervous system is altered with antenatal synthetic glucocorticoid treatment.
Young
Nicole A
NA
Behavioural Neuroscience Research Group, Department of Psychology, University of Calgary, Calgary, Alberta, Canada T2N 1N4.
Teskey
G Campbell
GC
Henry
Luke C
LC
Edwards
Heather E
HE
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000008:administration & dosage; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage; D004597:Electroshock / Q000009:adverse effects*; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage*; D006624:Hippocampus / Q000502:physiology*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D012737:Sex Factors; D050497:Stillbirth; D013997:Time Factors
D005938:Glucocorticoids; D003907:Dexamethasone; D001623:Betamethasone