EXPOSURE TO PRENATAL NICOTINE TRANSIENTLY INCREASES NEURONAL NICOTINIC RECEPTOR SUBUNIT ALPHA-7, ALPHA-4 AND BETA-2 MESSENGER-RNAS IN THE POSTNATAL RAT-BRAIN

This study determined the effects of prenatal nicotine exposure (2 mg/ kg/day) in Sprague-Dawley CD rats via subcutaneously implanted osmotic minipumps, during gestational days 7-21, on postnatal levels of neuro nal nicotinic receptor alpha 4, alpha 7 and 32 subunit messenger RNAs. Northern analysis of postnatal day 1, 7, 14 and 28 hippocampal/septal and cortical total RNA using alpha-[P-32]dCTP-labeled alpha 4, alpha 7 and beta 2 complementary DNA probes identified a single (5.7-kb) alp ha 7 messenger RNA, three (2.4-, 3.8- and 8.0-kb) alpha 4 messenger RN As and four (1.7-, 5.0-, 7.5- and 10.0-kb) beta 2 messenger RNAs. In c omparison to prenatal saline, prenatal nicotine produced several signi ficantly higher messenger RNA levels (cortical: 5.7-kb alpha 7, 2.4-, 3.8- and 8.0-kb alpha 4, 10.0-kb beta 2; hippocampal/septal: 2.4- and 8.0-kb alpha 4); these increases occurred predominantly on, but were n ot restricted to, postnatal day 14. Effects of nicotine were generally resolved by postnatal day 28. Collapsing the data across sex and age, a significant treatment effect indicated that hippocampal/septal and cortical 8.0-kb alpha 4 messenger RNA levels and 10.0-kb beta 2 messen ger RNA levels were significantly higher following prenatal nicotine e xposure. This is the first study indicating that prenatal nicotine pro duces alterations in developing postnatal rat neuronal nicotinic recep tor messenger RNA levels, possibly by premature stimulation of neurona l nicotinic receptors. These results further implicate the teratogenic potential of nicotine in postnatal neuronal development. (C) 1998 IBR O. Published by Elsevier Science Ltd.