Ferchmin P A, Rivera E, Eterović V A
Department of Biochemistry, Universidad Central del Caribe School of Medicine, Bayamon, PR 00960.
Pharmacol Biochem Behav. 1993 Aug;45(4):967-71. doi: 10.1016/0091-3057(93)90149-n.
alpha-Difluoromethylornithine (DFMO), a specific inhibitor of putrescine synthesis, is widely used in studies of polyamine function as well as clinically. We studied the effect of DFMO on the tendency to explore in the Greek cross maze that provides the rat with the choice to enter either white or black compartments. After a single injection of 400 mg/kg DFMO, the entries into white compartments were significantly decreased. A similar decrease had been observed previously with 200 mg/kg putrescine. Simultaneous administration of DFMO (400 mg/kg) and putrescine (200 mg/kg) resulted in decreased entries into both white and black compartments. When 400 mg/kg DFMO plus 400 mg/kg putrescine were injected, the entries into both compartments were further decreased and the time spent in white compartments was also decreased. This pattern mimicked that found with anxiogenic drugs. Injection of DFMO (400 mg/kg) produced no change in either putrescine, spermidine, or spermine concentration measured in brain cortex. Putrescine (200 mg/kg) plus DFMO produced the same transient increase in cortical putrescine as putrescine alone. We conclude that DFMO is mildly anxiogenic and that this activity is independent of its inhibition of putrescine synthesis.
α-二氟甲基鸟氨酸（DFMO）是腐胺合成的特异性抑制剂，广泛应用于多胺功能研究及临床。我们研究了DFMO对大鼠在希腊十字迷宫中探索倾向的影响，该迷宫为大鼠提供进入白色或黑色隔室的选择。单次注射400mg/kg DFMO后，进入白色隔室的次数显著减少。此前用200mg/kg腐胺也观察到类似的减少。同时给予DFMO（400mg/kg）和腐胺（200mg/kg）导致进入白色和黑色隔室的次数均减少。当注射400mg/kg DFMO加400mg/kg腐胺时，进入两个隔室的次数进一步减少，且在白色隔室停留的时间也减少。这种模式与焦虑症药物的情况相似。注射400mg/kg DFMO后，在大脑皮层中测得的腐胺、亚精胺或精胺浓度均无变化。腐胺（200mg/kg）加DFMO产生的皮层腐胺短暂增加与单独使用腐胺时相同。我们得出结论，DFMO具有轻度致焦虑作用，且这种活性与其对腐胺合成的抑制作用无关。
