Participation of the endogenous opioid system in the acquisition of a prenatal ethanol-related memory: effects on neonatal and preweanling responsiveness to ethanol.

The present study tested the involvement of the opioid system in the acquisition and expression of prenatal ethanol-related memories. We evaluated how this prenatal experience modulates ethanol self-administration in newborn rats, and preweanling's ingestion of the drug. During Gestational Days (GDs) 17-20, four groups of dams were treated with ethanol (2 g/kg) or water, followed immediately by naloxone (10 mg/kg) or saline administration. A fifth group received a similar dose of naloxone 20min before ethanol administration. On PD 1, pups were tested on an operant learning procedure to obtain milk or 3% ethanol. One hour later, an extinction session was performed. At Postnatal Days (PDs) 14 and 15, preweanlings representing each prenatal treatment were evaluated in an intake test with infusions of 5% ethanol or water. Prior to the intake test on PD14, preweanlings were administered naloxone (1 mg/kg), saline or remained untreated. In both tests, animals representative of both genders were utilized. One-day-old pups rapidly learned the operant behavior to gain access to milk. In contrast, only pups prenatally treated with ethanol (administered immediately before naloxone or saline injection) increased operant responding to gain access to ethanol. On an intake test at PDs 14 and 15, those animals prenatally exposed to naloxone 20 min before ethanol administration consumed significantly lower ethanol levels than the remaining prenatal ethanol groups. Postnatal treatment with naloxone diminished intake of all solutions at PD14. These results suggest that prenatal ethanol exposure facilitates neonatal operant learning reinforced by intraoral administration of ethanol and increases ethanol consumption during PDs 14-15. The endogenous opioid system apparently is involved in the acquisition of prenatal ethanol memories, which can modulate the reinforcing attributes of the drug in neonatal and preweanling rats.