Morphologic and behavioral effects of perinatal glucocorticoid administration

Male rats were infused with one of two doses of dexamethasone or saline on day 4 of life. Body, whole brain, hippocampal, and cerebellar weights were obtained at 10, 20 and 150 days of age, and the ability of the rats to acquire and reverse a spatial discrimination task was assessed at 90 days of age. Body weights and brain weights were severely and permanently suppressed in the high dose group (100 mg/kg), resulting in a 20% decrement from saline-injected controls in adulthood. Low dose (1 mg/kg) animals were transiently slowed in body and brain growth, but differences from controls were no longer detectable at 60 days of age. Both high dose and low dose animals were significantly impaired in acquisition and reversal of a spatial learning task in an open field water maze, and exhibited deficits characteristically seen in animals with hippocampal damage. The animals' swimming performance per se was unimpaired. It appears that even transient interruption of normal interactive sequences of brain development by the alteration of post-natal neurogenesis or gliogenesis by glucocorticoids results in a permanent behavioral deficit.