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.