Active avoidance behavior in the F₁ progeny of male rats exposed to cyclophosphamide prior to fertilization

The acquisition and extinction of a one-way avoidance task was studied in 30 day old F₁ progeny of male rats previously exposed to either acute or chronic treatment with cyclophosphamide (CP) prior to breeding with normal females. Chronic treatment (10 mg/kg/day x 5 days x 5 weeks) was given to adult F344 males followed by subsequent breeding with normal females (CP-S). Separate groups of males were given a single CP injection (10 mg/kg) and breeding with normal females was done at 7-9, 14-16 and 28-30 days following the CP treatment. F₁ progeny of males exposed to chronic CP or to a single CP treatment when bred 7-9 (females only) and 14-16 days post exposure (males and females) took significantly longer to reach the criterion for extinction. These progeny also responded significantly faster during extinction than progeny of the saline treated males. These findings support our earlier evidence of behavioral anomalies induced in the F₁ progeny of male rats exposed to CP prior to breeding and that this effect reflects damage in post-meiotic germ cells.