Developmental changes in nicotinic receptor mRNAs and responses to nicotine in the suprachiasmatic nucleus and other brain regions

Our previous studies demonstrated that nicotine induces c-fos expression in the suprachiasmatic nucleus (SCN) of the rat during a narrow developmental window occurring in the perinatal period. We have extended these observati ons by showing that c-fos cannot be induced in the adult SCN by nicotine ev en during the subjective night, when phase shifts do occur. In contrast to the SCN, significant induction of c-fos and NGFI-A was observed in the medi al habenula and paraventricular nucleus at all circadian times. In the feta l rat SCN we show that NGFI-A and junB are also induced by nicotine, but no t c-jun. To investigate whether changes in nicotinic acetylcholine receptor (nAChR) expression in the SCN may underlie this change in sensitivity duri ng the perinatal period, we examined nAChR mRNAs across this developmental period. By Northern analyses, alpha 2, alpha 3 and alpha 4 subunit mRNAs ar e relatively abundant in the fetal SCN but decline substantially in the adu lt. alpha 7 mRNA increases substantially while beta 2 mRNA is relatively ab undant throughout development. We also examine expression in the whole mous e brain beginning at embryonic day ii. Many mRNA sizes for nAChR subunits i n both the rat and mouse are characterized here for the first time by North ern analyses and some show very large changes in expression across developm ent. In particular, a small 1.4 kb alpha 2-related mRNA is highly expressed during early development, perhaps indicating an important novel function f or this subunit, (C) 1999 Elsevier Science B.V. All rights reserved.