Reproductive and sexual behavior changes in male rats exposed perinatally to picrotoxin

Previous studies in rats suggested that picrotoxin, a GABA(A) receptor antagonist, may cause long-term changes in male reproductive physiology and behavior in rats exposed during prenatal and postnatal periods. The present study has further examined this phenomenon. Wistar rat dams were dosed subcutaneously with 0.75 mg/kg picrotoxin in saline, or vehicle alone, during the perinatal period (day 19 of gestation, immediately after parturition, and once a day during the first 5 days of lactation). Birth weight and sexual maturation of pups were unchanged; however, plasma testosterone levels and sexual behavior was altered in male offspring. Although fertile, these males showed altered mating behavior in terms of a decrease in the mean number of mounts during a 30-min observation period with normal females. Some showed homosexual behavior when castrated and pretreated with exogenous estrogen. These findings suggest that perinatal exposure to picrotoxin alters sexual dimorphism in the developing rat brain, manifesting as altered reproductive performance and sexual behavior of males.