Ethanol neuro–behavioural teratogenesis in the guinea pig: behavioural dysfunction and hippocampal morphologic change

Abstract

Ethanol neuro–behavioural teratogenesis was studied in the guinea pig because of its extensive prenatal brain development, Our objective was to study, in the offspring of the guinea pig, behavioural and hippocampal morphologic effects produced by chronic maternal administration of 3 and 4 g ethanol kg body weight−1∙day−1. Pregnant guinea pigs received one of the following chronic treatments via intubation into the oral cavity: 3 or 4 g ethanol∙kg−1∙day−1 as two equally divided doses 2 h apart; isocaloric sucrose and pair feeding; or water. Five litters were obtained for each treatment. Locomotor activity rate was determined on postnatal days 10, 20, and 60, and testing of the spontaneous alternation task was conducted beginning on postnatal days 22 and 62. After behavioural testing, the hippocampus of the brain of randomly selected guinea pig offspring of each treatment group was assessed histologically by light microscopic examination of cresyl violet stained coronal sections. The 3 and 4 g ethanol∙kg−1∙day−1 regimens did not restrict maternal body weight gain or growth of the offspring. Both regimens increased locomotor activity rate in the offspring, which persisted into adulthood for the 4 g ethanol∙kg−1∙day−1 regimen. Neither ethanol regimen impaired spontaneous alternation, but the 4 g ethanol∙kg−1∙day−1 regimen increased the percent completed trials. Only the 4 g ethanol∙kg−1∙day−1 regimen produced structural injury in the hippocampus, consisting of a 25% decrease in the number of CA1 pyramidal neurons. The data demonstrate that the 4 g ethanol∙kg−1∙day−1 regimen produces more behavioural dysfunction and hippocampal morphologic change compared with the 3 g ethanol∙kg−1∙day−1 regimen.Key words: ethanol, teratogenesis, guinea pig, locomotor activity, spontaneous alternation, hippocampus, CA1 pyramidal neurons.