Prenatal Ethanol Exposure Increases Ethanol Reinforcement in Neonatal Rats

Abstract

Recent experimental findings indicate that newborn rats are quite susceptible to the reinforcing properties of ethanol (EtOH). The basis seems to be more pharmacological than gustatory, olfactory, or caloric as a single pairing of a surrogate nipple providing water with an intraperitoneal (i.p.) injection of EtOH results in conditioned attachment to an empty surrogate nipple. The present study tested whether prenatal exposure to moderate EtOH during late gestation would alter the neonatal rat's susceptibility to this source of EtOH reinforcement and/or EtOH metabolism. Pregnant females were given 1 g/kg EtOH or water intragastrically on gestational days (GD) 17 to 20 or were untreated. Rat pups delivered by cesarean section on GD 21 were exposed 3 to 4 hours later to a surrogate nipple providing water, either immediately following or 10 minutes before an i.p. injection of 0.0 (saline), 0.25, 0.5, or 0.75 g/kg EtOH (12.6%, v/v). Ethanol reinforcement was indicated by a significant increase in time attached to an empty surrogate nipple compared with unpaired and saline controls. Testing was conducted 90 minutes after conditioning took place. Blood ethanol levels (BELs) were also taken from subjects injected with identical doses of i.p. EtOH at 5 or 95 minutes after injection. Initial response to a surrogate nipple with water did not differ between groups. For neonates prenatally exposed to EtOH, significant reinforcement by all 3 doses of i.p. EtOH (0.25, 0.5, and 0.75) was found, whereas only the dose of 0.5 g/kg EtOH was reinforcing for neonates in the prenatal water condition and only 0.25 g/kg was reinforcing for pups from untreated dams. Blood ethanol levels after conditioning also differed as a function of prenatal treatment. These results suggest that prenatal EtOH exposure increases the range of EtOH doses capable of reinforcing effects. Intubations with water, however, eliminated the reinforcing strength of the lowest dose (0.25 g/kg) and shifted the dose-response curve to the right. This effect may be due to the stress of the intubation procedure. Ethanol metabolism was also affected by prenatal EtOH exposure. Pups derived from EtOH-treated dams had slower elimination of EtOH from the blood than all other groups at both the 0.5 and 0.75 g/kg i.p. doses.