Effects of perinatal cocaine exposure on open field behavior and the response to corticotropin releasing hormone (CRH) in rat offspring

Previous reports indicate that prenatal cocaine exposure alters specific behaviors and hypothalamic-pituitary-adrenal axis (HPA) function in the offspring. In most previous studies, cocaine was given via subcutaneous injections. However intravenous administration more closely mimics human cocaine abuse during pregnancy. Therefore, we investigated the effects of prenatal cocaine exposure via intravenous injection to the mothers on open field behavior and HPA axis function of the offspring. We hypothesized that prenatal cocaine exposure decreases immobility in a novel environment, and enhances the HPA response to stress. Dams received cocaine (COC) or vehicle (control, CON) intravenously from gestation day 8 to postnatal day (PD) 5. Behaviors were recorded in the open field on PD 28 (weanlings). As expected, perinatally cocaine-exposed offspring spent less time immobile and had a longer latency to entering the center zone. No other behavioral activities were different between the groups. On PD 43-50, adolescent male and female offspring received either corticotropin releasing hormone (CRH) or saline intravenously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and up to 60 min after injection. COC-exposed offspring of both sexes had higher basal CORT levels. Prenatal cocaine enhanced the CORT response to CRH/saline injections up to 60 min in males but not in females. These novel results show that perinatal administration of cocaine in a manner that most closely mimics human cocaine use has long-term effects on the offspring's behavioral response to stress and on HPA axis functions.