Ontogenesis of nicotinic acetylcholine receptors and presynaptic cholinergic neurons in mammalian brain

Abstract We find a significantly lower level of specific [ 3 H]nicotine binding in the fetal rat forebrain of 20 day gestational age as compared to adult rat tissue, and a progressive increase in the [ 3 H]nicotine binding in the early neonatal forebrain, reaching adult level at 14–28 days of age. The maximal binding sites (Bmax) for the brain [ 3 H]-nicotine binding at the ages of 3, 14 and 28 days were 36%, 74% and 98% respectively of the adult value. Neusurugatoxin (NSTX) was a potent inhibitor of [ 3 H]nicotine binding in the neonatal forebrain (IC 50 = 205, 81 and 103 nM at the 3, 14 and 28 days of age) as well as in the adult tissue (IC 50 = 79 nM). Both the choline acetyltransferase (ChAT) activity and high affinity uptake of [ 14 C]choline were not detectable or extremely low in the 1 week neonatal forebrain, and then increased progressively with age to reach the adult level at about 6 weeks of age. These data indicate that central nicotinic receptors may mature prior to the development of presynaptic cholinergic elements.