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

Alpha-Difluoromethylornithine (DFMO), a specific inhibitor of putresci ne synthesis, is widely used in studies of polyamine function as well as clinically. We studied the effect of DFMO on the tendency to explor e in the Greek cross maze that provides the rat with the choice to ent er either white or black compartments. After a single injection of 400 mg/kg DFMO, the entries into white compartments were significantly de creased. A similar decrease had been observed previously with 200 mg/k g putrescine. Simultaneous administration of DFMO (400 mg/kg) and putr escine (200 mg/kg) resulted in decreased entries into both white and b lack compartments. When 400 mg/kg DFMO plus 400 mg/kg putrescine were injected, the entries into both compartments were further decreased an d the time spent in white compartments was also decreased. This patter n 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 DF MO produced the same transient increase in cortical putrescine as putr escine alone. We conclude that DFMO is mildly anxiogenic and that this activity is independent of its inhibition of putrescine synthesis.