Mickley G A, Remmers-Roeber D R, Crouse C, Peluso R
Department of Psychology, Carnegie Hall, Baldwin-Wallace College, 275 Eastland Rd., Berea, OH 44017-2088, USA.
Pharmacol Biochem Behav. 2000 Jul;66(3):547-52. doi: 10.1016/s0091-3057(00)00250-1.
Brain N-methyl-D-aspartate (NMDA) glutamate receptors have been implicated as important mediators of both learning and neuronal development. The current study investigated how ketamine HCl (a well-known NMDA-receptor blocking drug) would influence taste-mediated conditioned motor responses in perinatal rats. Dams pregnant with E19 rat fetuses were injected with 0, 50, or 100 mg/kg ketamine HCl (IP). One-half hour later, a reversible spinal block was performed on the dam, and fetuses received an oral injection of 10 microl 0.3% Saccharin (SAC) or water while in utero. After the oral injection, fetuses received either saline or LiCl (81 mg/kg, IP). The uterus was replaced and, 2 days later (E21), rats received oral lavage with SAC. Rats in other litters were born via a normal vaginal delivery and were exposed to SAC on postnatal day 3 (P3). Observations of motor responses were recorded immediately after the oral lavage of SAC. If SAC had been paired with LiCl in utero, both E21 and P3 pups exhibited a conditioned suppression of orofacial movements (compared to controls). Both doses of ketamine significantly attenuated this taste-mediated conditioned motor response. These data reinforce the current conception of the fetus and neonate as sophisticated sensors and responders to the uterine and extrauterine environment. Further, our findings indicate a role for NMDA receptors in the formation of a conditioned motor response in fetal rats.
脑N-甲基-D-天冬氨酸（NMDA）谷氨酸受体被认为是学习和神经元发育的重要介质。本研究调查了盐酸氯胺酮（一种著名的NMDA受体阻断药物）如何影响围产期大鼠味觉介导的条件性运动反应。对怀有E19大鼠胎儿的母鼠腹腔注射0、50或100mg/kg盐酸氯胺酮。半小时后，对母鼠进行可逆性脊髓阻滞，胎儿在子宫内接受10微升0.3%糖精（SAC）或水的口服注射。口服注射后，胎儿接受生理盐水或氯化锂（81mg/kg，腹腔注射）。将子宫复位，2天后（E21），给大鼠用SAC进行口腔灌洗。其他窝的大鼠通过正常阴道分娩出生，并在出生后第3天（P3）接触SAC。在对SAC进行口腔灌洗后立即记录运动反应观察结果。如果SAC在子宫内与氯化锂配对，E21和P3幼崽均表现出对口面部运动的条件性抑制（与对照组相比）。两种剂量的氯胺酮均显著减弱了这种味觉介导的条件性运动反应。这些数据强化了目前关于胎儿和新生儿是子宫内和子宫外环境的复杂传感器和反应者的观念。此外，我们的研究结果表明NMDA受体在胎鼠条件性运动反应的形成中起作用。
