Maternal exposure to the antiepileptic drug vigabatrin affects postnatal development in the rat.
The objective was to investigate, in the rat, the effects of maternal exposure to vigabatrin (VGB) on the postnatal motor-cognitive behaviour of the offspring. We used an experimental evaluator-blind, placebo-controlled study in the rat. Ten pregnant rats were divided into five groups and treated with different doses of VGB (250, 500, 750, 1000 mg/kg/day) or placebo from gestation day (GD) 6 to GD10. After delivery, 56 pups (40 pups prenatally exposed to VGB and 16 pups exposed to placebo) were evaluated for motor-cognitive behaviour throughout postpartum day 40. At the end of testing sessions the animals were sacrificed and brain tissues processed for biochemical analysis of GABA levels. Body weight of pups and young rats whose mothers were treated with a dose of 750 mg/kg/day were significantly lower both at birth and during the whole postnatal life with respect to the control groups. Young rats of this group exhibited impaired performance in both the open-field and water maze tasks. Brain GABA contents were dramatically increased in this group of rats. No other significant nutritional, biochemical or behavioural changes were observed after treatments with doses of VGB lower than 750 mg/kg/day. The exposure to a dose of 1000 mg/kg caused abortion. Maternal exposure to VGB at relatively high doses (750 mg/kg/day) is likely to cause some important changes of the nutritional status during the pre- and postnatal life. Thus, the biochemical and cognitive abnormalities observed in this study could be related to some disturbances of brain development induced by malnutrition and/or to a disturbance of neuronal programming of the gabaergic system.
Lombardo
S A
SA
Department of Experimental and Clinical Pharmacology, Chair of Neuropsychopharmacology, School of Medicine, University of Catania, Viale A. Doria 6, I-95125 Catania, Italy.
Leanza
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Meli
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Lombardo
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Mazzone
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Vincenti
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Cioni
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D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008098:Litter Size / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010919:Placebos; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013997:Time Factors; D020888:Vigabatrin / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D010919:Placebos; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin