PRENATAL NICOTINE EFFECTS ON MEMORY IN RATS - PHARMACOLOGICAL AND BEHAVIORAL CHALLENGES

Cigarette smoking during pregnancy has been shown in a variety of stud ies to be associated with cognitive deficits in the children. Nicotine administration to rats during gestation has been found to cause subtl e cognitive effects in the offspring. Some individual differences in c ognitive impairment may be related to prenatal nicotine effects on nor adrenergic (NE) systems. In the current study, 10 Sprague-Dawley rat d ams were infused with approximately 2 mg/kg/day of nicotine ditartrate via osmotic minipumps and 10 control dams were exposed to vehicle-con taining minipumps from gestational day (GD) 4-20. Starting on postnata l day (PND) 50, the offspring were tested for T-maze rewarded spatial alternation with intertrial intervals of 0, 10, 20 or 40 s. There was a sex- and delay-dependent effect of prenatal nicotine exposure on T-m aze alternation. Nicotine-exposed males showed a significant deficit a t the 0 s delay. In radial-arm maze (RAM) acquisition training there w ere no significant nicotine effects. However, significant nicotine-rel ated effects were seen with subsequent behavioral and pharmacological challenges in the RAM. Changing the RAM testing location to an identic al maze in a different room elicited a significant choice accuracy def icit in the prenatal nicotine-exposed rats compared with controls. Acu te nicotine challenge did not cause any differential effects in the pr enatal nicotine and control groups. During the isoproterenol (beta-NE agonist) challenge phase there appeared a significant facilitation of choice accuracy and speeding of response in the prenatal nicotine expo sure group which was not seen in the control group. The alpha-NE agoni st phenylpropanolamine caused a significant deficit in control females but not in the females prenatally exposed to nicotine. No differentia l effects of the alpha-NE antagonist phenoxybenzamine were seen in the prenatal nicotine and control groups. Throughout RAM testing there wa s a significant sex effect with males having better choice accuracy th an females. These results demonstrate that the persisting cognitive ef fects of prenatal exposure to 2 mg/kg/day cause subtle effects in cogn itive performance which can be elicited with behavioral and pharmacolo gical challenge. These results also support previous studies suggestin g the involvement of NE systems in persisting effects of prenatal nico tine exposure.