Mickley G A, Lovelace J D, Farrell S T, Chang K S
Radiofrequency Radiation Division, Armstrong Laboratory (AL/OER), Brooks AFB, TX 78235-5324, USA.
Brain Res Dev Brain Res. 1995 Mar 16;85(1):119-27. doi: 10.1016/0165-3806(94)00202-b.
Rat fetuses (E18) can learn a taste aversion in utero if experience with a sweet flavor (saccharin = Sac) is followed by a malaise-producing injection of lithium chloride (LiCl). Here we report that this phenomenon can be significantly modulated by the type of anesthesia administered to the pregnant dam before the conditioning procedure. Dams were anesthetized with one of the following drugs or drug combinations: (1) sodium pentobarbital; (2) ketamine hydrochloride and xylazine; or (3) sodium pentobarbital and ketamine hydrochloride. While under the influence of these anesthetics, rat fetuses received pairings of Sac + LiCl or one of the following sets of oral and systemic (i.p.) control injections: Sac + Saline, H2O + LiCl; H2O + Saline. At age 15 days neonatal rats were given a taste preference test by allowing them to select nipples painted with either saccharin or vehicle (H2O). After weaning, rats were given an additional taste preference test where they were allowed to drink from bottles filled with either 0.30% saccharin or water. Neonates that received Sac + LiCl injections avoided saccharin-painted nipples while neonates that received control injections in utero preferred saccharin-painted nipples. Rats that acquired the taste aversion under the influence of ketamine showed a significantly stronger conditioned taste aversion on the nipple preference test than did those from dams injected with sodium pentobarbital. The conditioned taste aversion was not detectable later during the bottle preference test. Since ketamine blocks N-methyl-D-aspartate (NMDA) glutamate receptors, and these receptors have been implicated in neural plasticity during development, our data suggest that NMDA antagonism can potentiate fetal learning. Ketamine has been used as an obstetrical and pediatric anesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)
如果给孕鼠注射产生不适的氯化锂(LiCl)之前,让其接触甜味剂(糖精 = Sac),那么大鼠胎儿(胚胎期18天)在子宫内就能学会味觉厌恶。在此我们报告,在条件反射程序之前给怀孕母鼠施用的麻醉类型可显著调节这一现象。用以下一种药物或药物组合对母鼠进行麻醉:(1)戊巴比妥钠;(2)盐酸氯胺酮和赛拉嗪;或(3)戊巴比妥钠和盐酸氯胺酮。在这些麻醉剂的作用下,大鼠胎儿接受Sac + LiCl配对或以下口服和全身(腹腔注射)对照注射组合之一:Sac + 生理盐水、水 + LiCl;水 + 生理盐水。在15日龄时,通过让新生大鼠选择涂有糖精或赋形剂(水)的乳头来进行味觉偏好测试。断奶后,给大鼠进行额外的味觉偏好测试,让它们从装有0.30%糖精或水的瓶子中饮水。接受Sac + LiCl注射的新生大鼠避开涂有糖精的乳头,而在子宫内接受对照注射的新生大鼠则更喜欢涂有糖精的乳头。在氯胺酮作用下获得味觉厌恶的大鼠在乳头偏好测试中表现出比接受戊巴比妥钠注射的母鼠所生大鼠更强的条件性味觉厌恶。在后来的瓶子偏好测试中未检测到条件性味觉厌恶。由于氯胺酮可阻断N - 甲基 - D - 天冬氨酸(NMDA)谷氨酸受体,且这些受体与发育过程中的神经可塑性有关,我们的数据表明NMDA拮抗作用可增强胎儿学习能力。氯胺酮已被用作产科和儿科麻醉剂。(摘要截选至250字)