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.

Prenatal ethanol increases sucrose reinforcement, an effect strengthened by postnatal association of ethanol and sucrose.

Late prenatal exposure to ethanol recruits sensory processing of the drug and of its motivational properties, an experience that leads to heightened ethanol affinity. Recent studies indicate common sensory and neurobiological substrates between this drug and sweet tastants. Using a recently developed operant conditioning technique for infant rats, we examined the effects of prenatal ethanol history upon sucrose self-administration (postnatal days, PDs 14-17). Prior to the last conditioning session, a low (0.5 g/kg) or a high (2.5 g/kg) ethanol dose were paired with sucrose. The intention was to determine if ethanol would inflate or devalue the reinforcing capability of the tastant and if these effects are dependent upon prenatal ethanol history. Male and female pups prenatally exposed to ethanol (2.0 g/kg) responded more when reinforced with sucrose than pups lacking this antenatal experience. Independently of prenatal status, a low ethanol dose (0.5 g/kg) enhanced the reinforcing capability of sucrose while the highest dose (2.5 g/kg) seemed to ameliorate the motivational properties of the tastant. During extinction (PD 18), two factors were critical in determining persistence of responding despite reinforcement omission. Pups prenatally exposed to ethanol that subsequently experienced the low ethanol dose paired with sucrose, showed higher resistance to extinction. The effects here reported were not associated with differential blood alcohol levels across prenatal treatments. These results indicate that fetal ethanol experience promotes affinity for a natural sweet reinforcer and that low doses of ethanol are also capable of enhancing the positive motivational consequences of sucrose when ethanol and sucrose are paired during infancy.

Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure.

Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 µmol) or EtOH (0.02 µmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 µmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life.