Shemer A V, Azmitia E C, Whitaker-Azmitia P M
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794.
Brain Res Dev Brain Res. 1991 Mar 18;59(1):59-63. doi: 10.1016/0165-3806(91)90029-i.
Our previous studies with a tissue culture model of neuronal development have shown that the development of serotonin neurons is dependent, at least in part, on the stimulation of high affinity serotonin receptors. One receptor inhibits the outgrowth of neurons, while the other promotes it. The present study was therefore undertaken to replicate these findings in a whole animal model system. Pregnant Sprague-Dawley rats were treated from gestational day 12 until birth with 0.1, 1.0 or 3.0 mg/kg 5-methoxytryptamine (5-MT). The pups were assessed for serotonin outgrowth by the selective synaptosomal uptake of [3H]serotonin at postnatal days 1, 15 and 30 (D1, D15, D30). In addition, the pups were tested behaviorally for the neonatal serotonin syndrome at D5 (induced by quipazine), spontaneous alternation and open field activity at day 15 and lick suppression at day 30. At 1.0 mg/kg, the terminal outgrowth of serotonin neurons was inhibited, while the highest dose, 3.0 mg/kg, showed stimulation of outgrowth. The highest dose caused behavioral alterations which had abated by 30 days, while the intermediate dose (1.0 mg/kg) showed behavioral changes throughout. Interestingly, the lowest dose, 0.1 mg/kg, showed changes in uptake only at D1 and behavioral changes only at later timepoints, principally at D30. This suggests that serotonin not only plays a role in regulating the development of the neurons which produce it, but that it may also play a role in neurochemical imprinting--that is, changes in behavior in the adult may be due to changes in neurochemistry during development, even though that neurochemistry may have been corrected by the time the animal becomes an adult.
我们之前使用神经元发育的组织培养模型进行的研究表明，血清素神经元的发育至少部分依赖于高亲和力血清素受体的刺激。一种受体抑制神经元的生长，而另一种则促进其生长。因此，本研究旨在在全动物模型系统中重复这些发现。将怀孕的斯普拉格-道利大鼠从妊娠第12天至出生期间用0.1、1.0或3.0mg/kg的5-甲氧基色胺（5-MT）进行处理。在出生后第1、15和30天（D1、D15、D30），通过[3H]血清素的选择性突触体摄取来评估幼崽的血清素生长情况。此外，在D5对幼崽进行行为测试以检测新生儿血清素综合征（由喹哌嗪诱导），在第15天测试自发交替和旷场活动，在第30天测试舔舐抑制。在1.0mg/kg时，血清素神经元的终末生长受到抑制，而最高剂量3.0mg/kg则显示出对生长的刺激作用。最高剂量引起的行为改变在30天时有所减轻，而中间剂量（1.0mg/kg）则始终表现出行为变化。有趣的是，最低剂量0.1mg/kg仅在D1时显示摄取变化，仅在后期时间点（主要是D30）显示行为变化。这表明血清素不仅在调节产生它的神经元的发育中起作用，而且可能在神经化学印记中也起作用——也就是说，即使动物成年时神经化学可能已经恢复正常，但成年后的行为变化可能是由于发育过程中神经化学的变化所致。
