Neonatal experiences with ethanol intoxication modify respiratory and thermoregulatory plasticity and affect subsequent ethanol intake in rats.

Different studies have focused on the deleterious consequences of binge-like or chronic exposure to ethanol during the brain growth spurt period (third human gestational trimester) that in the rat corresponds to postnatal days (PDs) 3-10. The present study analyzed behavioral and physiological disruptions caused by relatively brief binge-like exposures (PDs 3, 5, and 7) with an ethanol dose lower (3.0 g/kg) than those frequently employed to examine teratological effects during this stage in development. At PD 9, pups were exposed to ethanol doses ranging between .0-3.0 g/kg and tested in terms of breathing patterns and thermoregulation. At PDs 11 and 12, ethanol intake was examined. The main findings were as follows: i) pre-exposure to the drug resulted in brief depressions in breathing frequencies and an exacerbated predisposition toward apneic episodes; ii) these effects were not dependent upon thermoregulatory alterations; iii) early ethanol treatment increased initial consumption of the drug which also caused a marked hypothermia that appeared to regulate a subsequent decrement in ethanol consumption; and iv) ethanol exposure retarded overall body growth and even one exposure to the drug (PD 9) was sufficient to reduce brain weights although there were no indications of microcephaly. In conjunction with studies performed during the late gestational period in the rat, the results indicate that relatively brief binge-like episodes during a critical window of brain vulnerability disrupts the respiratory network and exacerbates initial acceptance of the drug. In addition, ethanol treatments were not found to induce tolerance relative to respiratory and thermal disruptions.

Maternal manipulation during late gestation (GDs 17-20) enhances ethanol consumption and promotes changes and opioid mRNA expression in infant rats.

Fetal ethanol experience generates learning and memories capable to increase ethanol consummatory behaviors during infancy. Opioid system seems to be involved in mediating those alcohol-related behaviors. In this work, we proposed to study the impact of prenatal exposure to a moderate ethanol dose, upon ingestion of the drug and possible ethanol-induced molecular changes on opioid precursor peptides (POMC, Pro-enk and Pro-DYN) and receptors (MOR, DOR and KOR) mRNA expression, in hypothalamus. Pregnant rats received during gestational days (GDs) 17-20, a daily intragastric (i.g.) administration with 2g/kg ethanol or water. A third group of dams was left undisturbed during pregnancy (Unmanipulated group). Intake test was conducted at postnatal days (PDs) 14-15. Three groups of pups were performed: control (no intake test), water (vehicle) and 5% ethanol. At the end of intake test blood samples were taken to quantify blood ethanol concentrations (BECs) and hypothalamus sections were obtained to perform qRT-PRC assessment of opioid precursor peptides and receptors. The analysis of the consummatory responses (% of consumption) and pharmacokinetic profiles (BECs) suggested that maternal manipulation induced by i.g. intubations, during the last four days of gestation (whenever ethanol or water), are sufficient to induce infantile ethanol intake during infancy. Gene expression from the hypothalamus of unmanipulated group revealed that infantile ingestive experiences with ethanol can down-regulate expression of mRNA Pro-Dyn and up-regulate mRNA expression of MOR and KOR. Finally, MOR mRNA expression was attenuated by prenatal i.g. manipulation in pups exposed to 5% ethanol.