Department of Pharmaceutical Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Life Sci. 2010 Mar 27;86(13-14):482-7. doi: 10.1016/j.lfs.2010.02.007. Epub 2010 Feb 12.
Restricted somatic growth during fetal or early postnatal periods has been suggested to serve as a predictive indicator for neuroanatomical changes and behavioral impairments during adulthood. Here, the effects of d-amphetamine sulfate (AMPH) exposure during the brain growth spurt period on this potential indicator were evaluated.
Rats received 0, 5, 15 or 25mg/kg/day of AMPH via two daily intragastric intubations from PD4-9. Body weight data were collected every other day from PD1 to 21, and then weekly until PD59. On PD9, a subset of animals was terminated 90min after the last amphetamine treatment and the weights of the cortex, cerebellum, and brainstem were collected. Weights of these brain regions from young adult rats were also assessed on PD68.
AMPH exposure during early postnatal development limited somatic growth in a dose-related manner, with significantly lower body weights in animals assigned to the AMPH 25 and AMPH 15 groups. However, this was transient in nature, with no significant difference in weight observed after pups were weaned on PD21. Further, no differences in brain weight were observed at either age as a result of AMPH exposure.
These findings support the idea that developmental AMPH exposure transiently restricts somatic growth. Moreover, the lack of effect on brain weight shows that AMPH differentially affects somatic and brain growth. The current findings suggest that in addition to the immediate effects on body weight, amphetamine may alter the rate of growth, and increase the risk for weight-related adult diseases.
胎儿期或出生后早期的躯体生长受限被认为是成年后神经解剖结构变化和行为障碍的预测指标。本研究旨在评估脑生长突增期硫酸二苯丙胺(AMPH)暴露对这一潜在指标的影响。
从 PD4-9 开始,大鼠通过每日两次胃内插管接受 0、5、15 或 25mg/kg/天的 AMPH 处理。从 PD1 到 21 天,每隔一天收集体重数据,然后每周收集一次,直到 PD59 。在 PD9 ,一部分动物在最后一次 AMPH 处理后 90 分钟终止,并收集大脑皮质、小脑和脑干的重量。还评估了 PD68 年轻成年大鼠这些脑区的重量。
AMPH 暴露于早期新生发育过程中以剂量相关的方式限制了躯体生长,接受 AMPH 25 和 AMPH 15 处理的动物体重明显较低。然而,这种情况是短暂的,在 PD21 断奶后体重没有明显差异。此外,由于 AMPH 暴露,在任何年龄都没有观察到脑重的差异。
这些发现支持了这样一种观点,即发育性 AMPH 暴露会短暂地限制躯体生长。此外,对脑重没有影响表明,AMPH 对躯体和脑生长有不同的影响。目前的研究结果表明,除了对体重的直接影响外,安非他命还可能改变生长速度,增加与体重相关的成年疾病的风险。