Stanton M E
Neurotoxicology Division (MD-74B), United States Environmental Protection Agency, Research Triangle Park, NC 27711.
Neurotoxicol Teratol. 1991 Sep-Oct;13(5):515-24. doi: 10.1016/0892-0362(91)90059-6.
Triethyltin is an organotin compound that is known to produce neurotoxicity in both adult and developing organisms. Although this neurotoxicity has been documented with a variety of behavioral and biological measures, the effects of this compound on learning during early development have been less extensively studied. The present study reports four experiments that examined this question with an odor aversion learning paradigm in which pups received presentations of one odor paired with footshock and an alternate odor without shock. In Experiment 1, Long-Evans rat pups were injected IP on postnatal day 5 (PND 5) with either 0, 3 or 5 mg/kg TET and then tested for olfactory discrimination learning on PND 18. Only the 5-mg/kg dose impaired discrimination learning. In Experiment 2, PND 5 exposure to TET (5 mg/kg) disrupted olfactory learning on PND 18 but not on PND 12, whereas exposure on PND 10 disrupted learning at both ages of testing. In Experiment 3, PND 16 exposure to TET (5 mg/kg) also disrupted acquisition of olfactory learning on PND 18 but had no effect on retention of an olfactory discrimination that was acquired prior to TET exposure (i.e., on PND 14 and PND 15). Unconditioned responses to footshock were also unaffected by TET (Experiment 4). These findings indicate that neonatal exposure to TET impairs associative learning in developing rats and are discussed in relation to other studies of the developmental neurotoxicity of this compound.
三乙基锡是一种有机锡化合物,已知其在成年生物体和发育中的生物体中都会产生神经毒性。尽管这种神经毒性已通过多种行为和生物学指标得到记录,但该化合物对早期发育过程中学习的影响研究较少。本研究报告了四项实验,这些实验采用气味厌恶学习范式来研究这个问题,在该范式中,幼崽接受一种与足部电击配对的气味呈现以及另一种无电击的替代气味呈现。在实验1中,Long-Evans大鼠幼崽在出生后第5天(PND 5)腹腔注射0、3或5毫克/千克的三乙基锡,然后在PND 18进行嗅觉辨别学习测试。只有5毫克/千克的剂量损害了辨别学习能力。在实验2中,PND 5暴露于三乙基锡(5毫克/千克)会破坏PND 18时的嗅觉学习,但不会影响PND 12时的学习,而PND 10时的暴露会破坏两个测试年龄阶段的学习。在实验3中,PND 16暴露于三乙基锡(5毫克/千克)也会破坏PND 18时嗅觉学习的获得,但对在三乙基锡暴露之前(即PND 14和PND 15)获得的嗅觉辨别记忆没有影响。对足部电击的非条件反应也不受三乙基锡的影响(实验4)。这些发现表明,新生大鼠暴露于三乙基锡会损害其联想学习能力,并结合该化合物发育神经毒性的其他研究进行了讨论。