Levin E D, Briggs S J, Christopher N C, Rose J E
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Neurotoxicol Teratol. 1993 Jul-Aug;15(4):251-60. doi: 10.1016/0892-0362(93)90006-a.
In humans and animal models there is evidence that prenatal nicotine exposure causes lasting deficits in cognitive performance. The current study examined the cognitive effects of prenatal exposure of rats to 2 mg/kg/day of nicotine. This dose did not cause significant deficits in maternal weight gain, offspring litter size, or pup weight. The control offspring showed the normal ontogeny of spontaneous alternation from near chance (50%) performance to 80%-85% alternation. In contrast, the nicotine-exposed rats had the opposite progression with abnormally high alternation on days 22-30 and abnormally low alternation on days 35-52. Acquisition of choice accuracy performance on the radial-arm maze (RAM) was not altered in a major way by nicotine exposure. Minor nicotine-induced changes in choice accuracy were seen during the initial trials of acquisition. The nicotine exposed female offspring had a significantly longer response duration. Prenatal nicotine exposure did significantly alter the effects of subsequent drug challenges on choice accuracy performance. The nicotine-exposed male offspring were significantly more responsive to the amnestic effects of the nicotinic antagonist mecamylamine. In a subsequent challenge, the effects of the beta-adrenergic antagonist propranolol were examined. A significant dose-related impairment in choice accuracy was seen in the control rats. In contrast, the nicotine-exposed rats did not show any significant response to propranolol. This decreased responsiveness to adrenergic challenge parallels the reduction in adrenergic response to nicotine challenge we previously found in littermates to the rats of the current study. Prenatal nicotine exposure causes subtle alterations in cognitive performance that can be magnified by challenges of nicotinic and adrenergic systems.
在人类和动物模型中，有证据表明产前接触尼古丁会导致认知能力出现持久缺陷。本研究检测了大鼠产前接触2毫克/千克/天尼古丁的认知影响。该剂量并未导致母体体重增加、后代窝仔数或幼仔体重出现显著缺陷。对照后代显示出自发交替行为从接近随机（50%）表现正常发育至80%-85%交替。相比之下，接触尼古丁的大鼠则呈现相反的进展，在第22 - 30天交替异常高，而在第35 - 52天交替异常低。接触尼古丁对放射状臂迷宫（RAM）上选择准确性表现的习得没有产生重大改变。在习得的初始试验期间观察到了尼古丁引起的选择准确性的微小变化。接触尼古丁的雌性后代反应持续时间显著更长。产前接触尼古丁确实显著改变了后续药物激发对选择准确性表现的影响。接触尼古丁的雄性后代对烟碱拮抗剂美加明的遗忘效应反应显著更强。在随后的激发试验中，检测了β-肾上腺素能拮抗剂普萘洛尔的作用。在对照大鼠中观察到了与剂量相关的显著选择准确性损伤。相比之下，接触尼古丁的大鼠对普萘洛尔未表现出任何显著反应。这种对肾上腺素能激发反应性的降低与我们之前在本研究大鼠的同窝仔中发现的对尼古丁激发的肾上腺素能反应降低情况相似。产前接触尼古丁会导致认知表现出现细微改变，而烟碱和肾上腺素能系统的激发可使这些改变放大。
