Exposure To Nicotine During Pregnancy And Altered Learning And Memory In The Rat Offspring

Part1： The effects of nicotine during pregnancy on development ofoffspring brain1.1Objective: To determine the effects of nicotine during pregnancy on fetal andoffspring brain development.1.2Methods: Time-dated pregnant SD rats were randomly divided into two groups:control and nicotine group (n=16, each group). Rats were anesthetized with chloralhydrate, and an incision was made on the rat back to insert osmotic mini-pumps (Type2ML4, Alza Corp, Palo Alto, CA). Nicotine was administered to pregnant rats throughimplanted osmotic mini-pumps at6mg/Kg/day.The rats received saline as the control. Werandomly selected8rats from the two groups and measured the fetal body weight andbrain weight at day21of gestation. Other rats were allowed to give birth naturally. Pupswere kept with their mothers until weaning. At weaning, male and female pups wereseparated and transferred to cages where they were housed in groups of two. The offspring(8litters each group,5months old) body weight and brain weight were measured. Bloodgases and electrolytes were determined with a Nova analyzer; Plasma osmolality wasdetermined with an advanced digimatic osmometer.1.3Result: Exposure to nicotine during pregnancy significantly decreased fetal bodyweight and brain weight, decreased plasma pO2and SO2%level, increased plasma pCO2and Hb level. Others blood gas index (Na+、K+、Osmolality) were not changed. In addition,those biochemical values in the prenatal nicotine exposure offspring were not significantlydifferent from those of the control at5months of old in both sexes. Conclusion: Exposureto nicotine during pregnancy affected fetal and offspring brain development and blood values. Part2：The effects of nicotine during pregnancy on learning and memoryin adult offspring rat2.1Objective: To determine the effects of nicotine during pregnancy on learning andmemory in the adult offspring rat.2.2Methods: Time-dated pregnant SD rats were randomly divided into two groups:control and nicotine group (n=16, each group). The offspring were reared to five months.1) Learning and memory were tested with Morris water maze;2) mRNA level of NR1andα7nACh receptor in the hippocampus were measured by Real-Time PCR;3) Protein levelof NR1、 α7nAChR、 muscarinic receptors in the hippocampus were measured bywestern blot.2.3Result:1）The ability of learning and memory in the nicotine group wassignificantly decreased；2) The expression levels of mRNA and protein of NR1wereincreased in the hippocampus of the offspring exposed to prenatal nicotine (P<0.05);3）There was no significant difference in α7nAChR mRNA abundance in the hippocampus.However, the expression of the α7nAChR protein in the hippocampus of the PN offspringwas significantly decreased compared to that of the control (P<0.05)；There was nosignificant difference in expression of M1R, M3R, and M5R protein in the hippocampusbetween the two groups of offspring. Conclusion: Maternal nicotine during gestationinfluenced the ability of learning and memory in offspring associated with change is NR1and α7nACh receptor in the hippocampus.