High Corticosterone Levels in Prenatally Stressed Rats Predict Persistent Paradoxical Sleep Alterations

Abstract

Prenatal stress predisposes rats to long-lasting disturbances that persist throughout adulthood (e.g., high anxiety, dysfunction of the hypothalamo-pituitary-adrenal axis, and abnormal circadian timing). These disturbances parallel to a large extent those found in depressed patients, in which hypercortisolemia and sleep alterations may be related to stress-inducing events. We studied sleep-wake parameters in control and prenatally stressed adult rats (3-4 months old) and examined possible relationships with their corticosterone levels (determined at 2 months of age). Under baseline conditions, prenatally stressed rats showed increased amounts of paradoxical sleep, positively correlated to plasma corticosterone levels. Other changes include increased sleep fragmentation, total light slow-wave sleep time, and a slight decrease in the percentage of deep slow-wave sleep relative to total sleep time. During recovery sleep from acute restraint stress, all sleep changes persisted and were correlated with stress-induced corticosterone secretion. High corticosterone levels under baseline conditions as well as an acute stress challenge may thus predict long-term sleep-wake alterations in rats. Taken together with other behavioral and hormonal abnormalities in prenatally stressed animals, the pronounced changes in sleep-wake parameters that are similar to those found in depressed patients suggest that prenatal stress may be a useful animal model of depression.