Shepanek N A, Smith R F, Tyer Z E, Royall G D, Allen K S
Department of Psychology, George Mason University, Fairfax, VA 22030.
Neurotoxicol Teratol. 1989 Sep-Oct;11(5):441-6. doi: 10.1016/0892-0362(89)90021-4.
Pregnant Long-Evans hooded rats were dosed subcutaneously with 1 or 5 mg/kg/day naloxone hydrochloride, or an equal volume of vehicle, from gestational Day 4 (GD4) through GD19. Offspring were assessed for development of righting reflex, negative geotaxis, and open field activity, and for acquisition of a Warden maze; offspring sacrificed at postnatal Day (PND) 21 were assessed for several parameters of cerebellar, hippocampal, and motor cortical morphology. Five mg/kg/day naloxone accelerated development of negative geotaxis and righting reflex, while 1 mg/kg/day naloxone tended to slow development. Low dose females had significantly more errors than controls on the first day of maze learning. The high dose group had a significantly higher concentration of granule cells in the curvature of the dentate gyrus than controls; other neuroanatomical measures were unaffected by dosing. These findings confirm and extend previous work indicating that prenatal exposure to naloxone may alter neurobehavioral development in the rat.
从妊娠第4天(GD4)至GD19,对怀孕的长 Evans 有帽大鼠皮下注射1或5mg/kg/天的盐酸纳洛酮,或等体积的赋形剂。评估后代的翻正反射、负趋地性和旷场活动的发育情况,以及在Warden迷宫中的习得情况;对出生后第21天(PND21)处死的后代进行小脑、海马和运动皮层形态学的几个参数评估。5mg/kg/天的纳洛酮加速了负趋地性和翻正反射的发育,而1mg/kg/天的纳洛酮则倾向于减缓发育。低剂量组雌性大鼠在迷宫学习的第一天比对照组有更多的错误。高剂量组齿状回弯曲处颗粒细胞的浓度显著高于对照组;其他神经解剖学指标不受给药影响。这些发现证实并扩展了先前的研究工作,表明产前暴露于纳洛酮可能会改变大鼠的神经行为发育。