The effect of prenatal ethanol exposure on pituitary-adrenal function in adult offspring was assessed by measuring corticosterone (CS) levels in plasma following exposure to two forms of footshock stress, intermittent and continuous, and after administration of 20 mg/kg of morphine. The footshock experiments were conducted at two time points in the circadian pituitary-adrenal cycle. Prenatally ethanol-exposed (E) rats had higher levels of CS than pair-fed and normal controls following intermittent footshock when tested at the crest of the CS circadian rhythm. However, this difference was not present when intermittent footshock was presented at the trough of the circadian cycle. At either time of day, there were no differences among the prenatal treatment groups in the basal condition or following continuous footshock. In addition, E rats had significantly higher levels of plasma CS than controls following morphine. Plasma adrenocorticotropin (ACTH) levels were measured after intermittent footshock at the crest of the circadian rhythm and were significantly higher in E rats than in controls. These results extend our previous reports of enhanced activation of the hypothalamo-pituitary-adrenal axis in response to other stressors as well as to ethanol in adult rats exposed to ethanol in utero. They also confirm that E rats are differentially hyperresponsive only to intermittent footshock stress, not to continuous footshock, as we had found to be the case when the analgesia induced by these two stressors was the dependent measure.

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Long lasting effects of perinatal ethanol exposure were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet ad libitum or pair-fed the isocaloric control diet during gestation weeks 2 and 3 or during postnatal week 1. Fetal exposure to ethanol reduced body weight of pups at birth unless the ethanol diet was supplemented with casein; neonatal exposure to the ethanol or pair-fed diets, casein supplemented or not, reduced pup weights until day 21 postnatally when weights of all fetally or neonatally exposed pups were normal. Between 52 and 120 days of age females were tested for pituitary-adrenal and temperature responses to a challenge dose of ethanol. Prenatally ethanol-exposed rats showed significantly higher plasma corticosterone titers and developed a greater hypothermia in response to an intraperitoneal injection of ethanol (0.75--1.5 g/kg) than did pair-fed controls. Similar responses enhancement did not occur in the postnatally ethanol-exposed rats. Temporal patterns of blood ethanol levels after an intraperitoneal injection of ethanol (1.5 g/kg) were similar in prenatally ethanol-exposed females and their pair-fed controls. The data indicate that exposure to ethanol in utero exerts persistent effects on the offspring, rendering them more responsive to the hypothermic and pituitary-adrenal activating effects of alcohol as adults.