ALPHA-DIFLUROMETHYLORNITHINE DOES NOT ANTAGONIZE THE BEHAVIORAL-EFFECTS OF PUTRESCINE

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.