Effect of perinatal alcohol exposure on ibotenic acid-induced excitotoxic cortical lesions in newborn hamsters.
Alcohol is one of the most common noxious substance to which fetuses are exposed. The aim of the study was to determine the effects of in utero alcohol exposure on excitotoxin-induced neuronal migration disorders. Female hamsters received alcohol (7%) for 3-5 mo or for the last 9-12 d of gestation. Alcohol diet was continued for 5 d during lactation in both groups. Drinking behavior was monitored. Peak plasma alcohol levels were 104+/-12 mg/dL and 225+/-6 mg/dL after 30 min for hamsters receiving an intragastric dose of 3 mL or 5 mL alcohol, respectively. At birth, pups received intrapallial injections ibotenic acid (1 ng, 100 ng, or 10 microg). Histology and N-methyl-D-aspartic acid (NMDA) receptor labeling by 3H-MK-801 in the pups cortices were studied. Short-term-alcohol-exposed pups had normal body and brain weights at birth, but their body growth was retarded postnatally. Ibotenic acid induced similar neuronal migration impairments in control and alcohol-exposed pups (nodular heterotopia in the white matter and/or deep cortical layers, subpial ectopia, and micro- or polymicrogyria). The size of lesions induced by 100 ng ibotenic acid was increased in alcohol-exposed pups; the 10 microg dose was lethal. The density of 3H-MK-801 binding sites was similar in the three groups, indicating that exacerbated ibotenic acid excitotoxicity in alcohol-exposed pups did not result from increased NMDA receptor density. This study shows that alcohol exposure at levels that do not induce neuron migration disorders is sufficient to enhance the effects of the hypoxia-ischemia mimicking effects of ibotenic acid.
Adde-Michel
Christine
C
UPRES EA 2122, School of Medicine and Pharmacy, Rouen University, Rouen, France.
Hennebert
Olivier
O
Laudenbach
Vincent
V
Marret
Stéphane
S
Leroux
Philippe
P
D000435:Alcoholic Intoxication; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000473:pathology; D002465:Cell Movement; D002492:Central Nervous System Depressants / Q000009:adverse effects; D006224:Cricetinae; D004327:Drinking Behavior; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D000860:Hypoxia; D007051:Ibotenic Acid / Q000378:metabolism / Q000494:pharmacology*; D007511:Ischemia; D007774:Lactation; D008647:Mesocricetus; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors
D002492:Central Nervous System Depressants; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D000431:Ethanol