Effect of nicotine administration on development of muscarinic receptor in central nervous system of rat neonate

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Rat fetuses or neonates were exposed to nicotine by administering nicotine to pregnant or lactating dams to estimate effects of nicotine on the development of cholinergic nervous system in brain of rat neonates. Since up-regulation of nicotinic receptor in rat neonates by nicotine administration has been already shown, we focussed on muscarinic receptor.1) We employed [^3H] QNB as a ligand to estimate muscarinic receptor. The level of muscarinic receptor in cerebral cortex started to develop just after birth and linearly increased to reach adult level 5 weeks after birth. Cerebellum showed a similar time course of muscarinic receptor development. However, in midbrain and hippocampus the level reached 80 % and in brainstem it reached 100 % of the adult level at 2 weeks after birth.2) We used pirenzepine as M1 specific and AF-DX116 as M2 specific ligands to examine the proportion of subtype of muscarinic receptor. Cerebral cortex and hippocampus were M1 dominant whereas cerebellum, midbrain and brainstem were M2 dominant tissues.3) We investigated the development of choline transporter, which is a specific marker for cholinergic post-synaptic terminal, by using [^3H] hemicholinium-3. Choline transporter in cerebral cortex started to develop after birth and reached 80 % of the adult level at 2 weeks after birth, as similarly seen in muscarinic receptor development in midbrain or hippocampus.4) Nicotine administration delayed the development of muscarinic receptor in cerebral cortex and cerebellum and delayed also that of choline transporter. These delays caught up with the normal time course at 5 weeks after birth.In conclusion, the present study demonstrates that perinatal nicotine treatment causes a developmental delay of muscarinic nervous system in rat neonates. These data can help us to understand one possible mechanism of the toxicity of cigarette smoking, as it related to brain development and the cause of neurological disorders