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

通过给予妊娠或哺乳期母鼠尼古丁，使大鼠胎仔或新生鼠暴露于尼古丁，以评估尼古丁对新生鼠脑胆碱能神经系统发育的影响。由于尼古丁给药可上调新生大鼠的烟碱受体，因此我们将重点放在毒蕈碱受体上。1）我们采用[^3H] QNB作为配体来估计毒蕈碱受体。大脑皮层M受体水平在出生后即开始发育，出生后5周呈线性上升，达到成人水平。小脑表现出类似的毒蕈碱受体发育的时间过程。2）以哌仑西平为M1特异性配体，AF-DX116为M2特异性配体，检测M1受体亚型的比例。大脑皮层和海马是M1优势组织，而小脑、中脑和脑干是M2优势组织。3）我们利用[^3H] hemicholinium-3研究了胆碱转运体的发育，胆碱转运体是胆碱能突触后末端的特异性标记物。大脑皮层胆碱转运体在出生后开始发育，在出生后2周达到成人水平的80%，与中脑或海马的毒蕈碱受体发育相似。4）尼古丁给药延迟了大脑皮层和小脑中毒蕈碱受体的发育，也延迟了胆碱转运体的发育。这些延迟赶上了正常的时间进程，在5周后birth.In结论，本研究表明，围产期尼古丁治疗导致发育延迟的新生大鼠毒蕈碱神经系统。这些数据可以帮助我们了解吸烟毒性的一种可能机制，因为它与大脑发育和神经系统疾病的原因有关

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