Renaud Samantha M, Fountain Stephen B
Department of Psychological Sciences, Kent State University, Kent, OH 44242-0001, USA.
Neurotoxicol Teratol. 2016 Jul-Aug;56:47-54. doi: 10.1016/j.ntt.2016.06.002. Epub 2016 Jun 7.
This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4days of massed training (20patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a "violation element" of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation.
本研究调查了一代大鼠在青春期接触尼古丁是否会损害后代的认知能力。亲代F0代的雄性和雌性大鼠在出生后第25 - 59天(P25 - 59)的青春期期间,每天腹腔注射两次,每次注射1.0mg/kg尼古丁或等量体积的生理盐水,持续35天。成年后,接触尼古丁的雄性和雌性大鼠与生理盐水对照的雄性和雌性大鼠配对繁殖。本实验仅使用雌性后代。F0代接触尼古丁的繁殖者的一半后代和F0代生理盐水对照大鼠的一半后代在P25 - 59的青春期期间每天腹腔注射两次,每次注射1.0mg/kg尼古丁。其余大鼠在同一时期每天注射两次生理盐水。为了评估尼古丁暴露对复杂认知学习能力的跨代影响,对F1代大鼠进行训练,使其在串行多项选择(SMC)任务中执行高度结构化的序列模式。从P95开始,F1代大鼠接受4天的集中训练(每天20个模式),随后进行间隔训练(每天10个模式),或者只进行间隔训练。观察到青春期尼古丁暴露的跨代影响表现为学习模式的“违反元素”时难度更大,这表明大鼠在将多个连续元素编码和记忆为复合或构型线索的能力方面受损。结果表明,对于接受集中训练的大鼠,F0代父母在青春期也接触过尼古丁的F1代青春期接触尼古丁的大鼠,在学习违反元素方面比仅在F1代经历青春期尼古丁暴露的大鼠表现更差。因此,一代大鼠在青春期接触尼古丁会导致下一代出现认知障碍。