Kelly S J, Black A C, West J R
Department of Psychology, Barnwell College, University of South Carolina, Columbia.
J Pharmacol Exp Ther. 1989 Jun;249(3):798-804.
Rats were exposed to ethanol from postnatal day 4 to day 10, using an artificial rearing procedure. One group received ethanol administered by a cyclic regimen, which resulted in high peak blood ethanol concentrations (BACs). Another group received the same daily dose of ethanol using a regimen which resulted in stable, moderate BACs. Two control groups consisted of rats reared artificially but not exposed to alcohol and rats reared normally by dams. All rats were raised to adulthood. Approximately half the rats were tested for behavioral activity levels and then sacrificed in order to assay the hippocampus for levels of cyclic GMP and protein after incubation with bethanechol (a muscarinic cholinergic agonist). The remaining rats were sacrificed and their hippocampi were assayed for muscarinic cholinergic receptors and protein content. Exposure to cyclic BACs with high peaks but not exposure to stable moderate BACs resulted in greater behavioral activity levels in both sexes and also a greater cyclic GMP responsiveness to a muscarinic cholinergic agonist. Furthermore, exposure to cyclic BACs with high peaks resulted in a significantly larger dissociation constant and a greater number of muscarinic cholinergic receptors. There were no differences among groups or sexes in protein content of the hippocampus. There were no interactions of the alcohol treatment with sex. Thus, in adult rats, exposure to alcohol during the brain growth spurt results in an increase in the dissociation constant and number of muscarinic cholinergic receptors in the hippocampus.
采用人工饲养程序，从出生后第4天至第10天让大鼠接触乙醇。一组接受通过循环给药方案给予的乙醇，这导致血液乙醇浓度（BAC）出现高峰值。另一组使用导致稳定、中等BAC的给药方案接受相同每日剂量的乙醇。两个对照组包括人工饲养但未接触酒精的大鼠以及由母鼠正常饲养的大鼠。所有大鼠均饲养至成年。大约一半的大鼠接受行为活动水平测试，然后处死，以便在用氨甲酰甲胆碱（一种毒蕈碱型胆碱能激动剂）孵育后测定海马体中的环磷酸鸟苷（cGMP）水平和蛋白质水平。其余大鼠被处死，并对其海马体进行毒蕈碱型胆碱能受体和蛋白质含量测定。暴露于高峰值的循环BAC而非稳定的中等BAC导致两性的行为活动水平更高，并且对毒蕈碱型胆碱能激动剂的cGMP反应性也更高。此外，暴露于高峰值的循环BAC导致解离常数显著增大以及毒蕈碱型胆碱能受体数量增加。各组之间以及两性之间在海马体蛋白质含量方面没有差异。酒精处理与性别之间没有相互作用。因此，在成年大鼠中，在脑发育快速期接触酒精会导致海马体中毒蕈碱型胆碱能受体的解离常数和数量增加。
