Alterations in hippocampal cholinergic receptors and hippocampal behaviors after early exposure to nicotine

Mice were exposed to nicotine prenatally by injecting the mother with 1.5 mg/kg nicotine SC twice daily on gestation days 9-18 (PreN mice) or neonatally by daily SC injections of 1.5 mg/kg nicotine on postnatal days 2-21 (NeoN mice). At age 50 days, hippocampal muscarinic receptors S_max of PreN and NeoN mice were 58% and 79% above control, respectively (p < 0.01); K_d was unaffected by early nicotine exposure. Eight-arm maze performance of nicotine-exposed animals fell behind control level. Both PreN and NeoN made approximately 10% less correct responses in the first eight trials than controls throughout the test period (p < 0.01). By the last day of testing, PreN needed 23% and NeoN 31% more trials than controls to enter all arms (p < 0.001). In addition, PreN needed 35 and NeoN 42% more days than controls to reach criterion (p < 0.05). Similarly, while 61% of controls reached criterion by day 6 only 17% of PreN and 25% of NeoN reached criterion (p < 0.01). In the Morris maze, PreN needed from 43-119% more time to reach the platform (p < 0.001). In the spatial probe test, PreN animals made 35% fewer crosses over the area of the missing platform (p < 0.001). The study suggests that nicotine administered to the fetus or neonate alters septohippocampal chemistry and induces deficits in hippocampus-related behaviors. The possible reversal of the behavioral changes by manipulating the cholinergic innervations should be the subject of future investigations.