Development and behavioral outcomes of perinatal inhibition of ornithine decarboxylase.

Rats were treated with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), at a dose of 200 mg/kg/day SC, either prenatally (to the mothers, on days 16 to 20 of gestation) or neonatally (to the pups, on days 1 to 10 after birth). At this dose level neither maternal reproductive performance (prenatal treatment) nor gain in body weight on the part of offspring were affected. Earlier developmental alterations were rapidly overcome. Prenatally-treated rats proved less active than controls in the open field, performed better in passive avoidance retention (both preweaning and postweaning), and had a shorter post-ejaculatory interval in the male copulatory test. Postnatally-treated rats performed better than controls in two-way active avoidance conditioning, and in passive avoidance retention (as adults). Reproductive performance of the treated female offspring was similar to that of controls. ODC activity in brains of DFMO-exposed offspring was substantially inhibited throughout treatment (-72 to -41%, compared with respective controls), but showed a strong rebound after termination of treatment (up to +400%, compared with respective controls). These results show that partial inhibition of ODC activity during a limited period of the perinatal life has no adverse effect on the overall behavioral development of rats: indeed, some performances are actually improved. This being the most likely due to a rebound ODC hyperactivity after termination of treatment, when brain maturation is still in progress.