Bell J M, Madwed D S, Slotkin T A
Neuroscience. 1986 Oct;19(2):457-64. doi: 10.1016/0306-4522(86)90274-5.
The roles of ornithine decarboxylase and the polyamines in behavioral development were examined through the use of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase. alpha-Difluoromethylornithine was administered either prenatally during gestation (days 15-17) or postnatally (days 1-20) to examine critical periods of sensitivity. Prenatal alpha-difluoromethylornithine administration resulted in a deficit in early sensorimotor ontogeny: latencies in surface righting reflex (postnatal days 1-5) and negative geotaxis (postnatal days 5-8) were prolonged, and time spent pivoting (postnatal days 7, 9, and 11) was reduced. In contrast, postnatal alpha-difluoromethylornithine primarily influenced later maturing, complex integrative behaviors such as swimming and open field activity. Thus, the behavioral effects of alpha-difluoromethylornithine exposure are highly dependent upon the age at which the drug is administered, a finding in keeping with the participation of the ornithine decarboxylase/polyamine system in cell replication and differentiation during discrete periods of neural development. The behavioral consequences of ornithine decarboxylase inhibition during these critical periods are thus related primarily both to the timetable for cellular maturation in each brain region.
通过使用α-二氟甲基鸟氨酸（一种鸟氨酸脱羧酶的特异性不可逆抑制剂），研究了鸟氨酸脱羧酶和多胺在行为发育中的作用。在妊娠期间（第15 - 17天）或出生后（第1 - 20天）给予α-二氟甲基鸟氨酸，以检查敏感的关键时期。产前给予α-二氟甲基鸟氨酸导致早期感觉运动发育迟缓：表面翻正反射（出生后第1 - 5天）和负趋地性（出生后第5 - 8天）的潜伏期延长，旋转时间（出生后第7、9和11天）减少。相比之下，出生后给予α-二氟甲基鸟氨酸主要影响后期成熟的复杂整合行为，如游泳和旷场活动。因此，α-二氟甲基鸟氨酸暴露的行为效应高度依赖于给药时的年龄，这一发现与鸟氨酸脱羧酶/多胺系统在神经发育的离散时期参与细胞复制和分化相一致。因此，在这些关键时期抑制鸟氨酸脱羧酶的行为后果主要与每个脑区细胞成熟的时间表有关。
