Effects of ethanol exposure in a familiar or isolated context during infancy on ethanol intake during adolescence.

Early exposure to ethanol affects ethanol intake later in life. This early experience encompasses exposure to social stimuli and the pharmacological and orosensory properties of ethanol. The specific contribution of each type of stimulus to subsequent ethanol intake remains unknown. We assessed the intake of various concentrations of ethanol in a familiar or isolated context during infancy and the lingering effects of this experience on ethanol intake during adolescence. On postnatal day 3 (PD3), PD7, and PD11, rats were given 5% ethanol or water in a nursing or isolated context (Experiments 1 and 2). Intake tests (ethanol vs. water) were conducted during adolescence. Experiment 2 matched the amount of fluid ingested during infancy in both contexts and subsequently tested ethanol consumption during adolescence. The results revealed a facilitative effect of the nursing context on fluid intake during the tests in infancy. Pups stimulated with ethanol but not water in the isolated context exhibited an increase in ethanol consumption during adolescence. This effect disappeared when the isolated infants were matched to receive the same amount of ethanol ingested by their nursed counterparts. In Experiment 3, isolated infant rats were exposed to different ethanol concentrations (.0%, 2.5%, 5.0%, and 10.0%), and drug consumption was tested during adolescence. This exposure increased adolescent ethanol intake, regardless of the alcohol concentration (Experiment 3). The common denominators that resulted in enhanced ethanol intake during adolescence were preexposure to ethanol via active consumption of the drug that induced a low-to-moderate level of intoxication in an isolated context.

Neonatal sensitization to ethanol-induced breathing disruptions as a function of late prenatal exposure to the drug in the rat: modulatory effects of ethanol's chemosensory cues.

Preclinical and clinical studies have systematically demonstrated abrupt changes in fetal respiratory patterns when the unborn organism is exposed to the effects of maternal ethanol intoxication. In subprimates, chronic exposure to this drug during gestation and infancy results in marked alterations of the plasticity of the respiratory network. These alterations are manifested in terms of an early incapability to overcome deleterious effects of hypoxic events as well as in terms of sensitization to ethanol's depressant effects upon breathing patterns. It has also been demonstrated that near term rat fetuses process ethanol's chemosensory cues when the drug contaminates the amniotic fluid and that associative learning processes occur due to the temporal contiguity existing between these cues and different ethanol-related physiological effects. In the present study during the course of late gestation (gestational days 17-20), pregnant rats were intragastrically administered with either 0.0 or 2.0 g/kg ethanol. Seven-day-old pups derived of these dams were evaluated in terms of respiration rates (breaths/min) and apneas when subjected to different experimental conditions. These conditions were defined by postnatal exposure to the drug (intragastric administrations of either 0.0, 0.5, 1.0 or 2.0 g/kg ethanol), postadministration time of evaluation (5-10 or 30-35 min) and olfactory context at test (no explicit ambient odor or ethanol ambient odor). The results, obtained via whole body plethysmography, indicated that brief prenatal experience with the drug sensitized the organisms to ethanol's depressant effects particularly when employing the higher ethanol doses. In turn, presence of ethanol odor at test potentiated the above mentioned respiratory alterations. Prenatal treatment with ethanol was not found to alter pharmacokinetic profiles resulting from postnatal exposure to the drug or to affect different morphometric parameters related with lung development. These results indicate that even brief exposure to the drug during late gestation is sufficient to sensitize the organism to later disruptive effects of the drug upon breathing responsiveness. These deficits are potentiated through the re-exposure to the olfactory context perceived in utero which is known to be associated with ethanol's unconditioned effects. As a function of these observations it is possible to suggest a critical role of fetal sensory and learning capabilities in terms of modulating later ethanol-related breathing disruptions.

Social isolation and stress related hormones modulate the stimulating effect of ethanol in preweanling rats.

Preweanling rats are highly sensitive to the locomotor stimulation induced by relatively high ethanol doses. In adult mice this ethanol effect is modulated by stress. The goal of the present study was to analyze the role of stress and corticosterone in the stimulating effect of ethanol in preweanling rats. In Experiment 1 15-day-old rats were separated from the mother during a period of 4h in which subjects remained isolated or paired with a littermate. In a third condition pups remained in the home-cage with the dam. After this isolation period pups were given ethanol (0 or 2.5 g/kg) and were tested in a novel environment. Previous data have shown that a similar period of isolation is enough to increase corticosterone levels in preweanling rats. Experiment 2 evaluated the effect of exogenous administration of corticosterone (0, 3 or 6 mg/kg) along with ethanol, and Experiment 3 tested ethanol-mediated locomotor activation in adrenalectomized preweanling rats. The last experiment aimed to test the role of corticotropic releasing factor 1 (CRF1) receptors in locomotion induced by ethanol in isolated pups. According to our results there is a synergism between stress or corticosterone and ethanol in preweanling rats. The interaction between stress (induced by social isolation) and ethanol seems to be mediated by CRF, since blockade of CRF1 receptors cancelled the effect of ethanol in isolated pups. This study highlights the importance of considering stress as a possible intervening variable in studies evaluating ethanol effects in developing animals when maternal separation is used in the experimental procedure.