The Neuroscience Program, Baldwin Wallace University, 275 Eastland Rd., Berea, OH, 44017.
Dev Psychobiol. 2014 Apr;56(3):435-47. doi: 10.1002/dev.21110. Epub 2013 Mar 26.
The etiology of schizophrenia's cognitive symptoms may have its basis in prenatal alterations of glutamate N-methyl-D-aspartate (NMDA) receptor functioning. Therefore, the current study investigated the effects of ketamine (an NMDA receptor blocking drug) on both a conditioned taste aversion (CTA) and latent inhibition (LI; a model of attentional capacity) in rat fetuses. We first sought to determine if a CTA could be diminished by nonreinforced preexposure to a CS in fetal rats (i.e., LI). We injected E18 pregnant Sprague-Dawley rats with 100% allicin (garlic taste) or an equal volume of saline. Some of the pregnant dams also received ketamine (100 mg/kg, i.p.). One day later (E19), the dams received a second injection of the CS, followed by either lithium chloride (the US) or saline. Finally, on E21 pups received oral lavage with allicin and observations of ingestive orofacial motor responses were recorded. When allicin had been paired with LiCl in utero, E21 fetuses exhibited a conditioned suppression of orofacial movements, indicative of an aversion to this taste. Preexposure to the garlic taste on E18 produced a LI of this CTA. Ketamine significantly disrupted the formation of the CTA and had some impact on LI. However, the direct effect of ketamine on LI is less certain since the drug also blocked the original CTA.
精神分裂症认知症状的病因可能源于胎儿期谷氨酸 N-甲基-D-天冬氨酸（NMDA）受体功能的改变。因此，本研究探讨了氯胺酮（一种 NMDA 受体阻断剂）对胎鼠条件味觉厌恶（CTA）和潜伏抑制（LI；注意力容量模型）的影响。我们首先试图确定未强化的 CS 预暴露是否会降低胎鼠的 CTA（即 LI）。我们给 E18 天孕龄的 Sprague-Dawley 大鼠注射 100%大蒜素（大蒜味）或等量生理盐水。一些孕鼠还接受了氯胺酮（100mg/kg，腹腔注射）。一天后（E19 天），给母鼠注射第二剂 CS，然后注射氯化锂（US）或生理盐水。最后，在 E21 天，给幼鼠进行大蒜素口服灌洗，并记录摄取性口面部运动反应。当大蒜素与 LiCl 在子宫内联合使用时，E21 胎鼠表现出对口部运动的条件抑制，表明对这种味道有厌恶感。E18 天对大蒜味的预暴露产生了 CTA 的 LI。氯胺酮显著破坏了 CTA 的形成，对 LI 也有一定影响。然而，氯胺酮对 LI 的直接影响不太确定，因为该药物也阻断了原始的 CTA。
