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  • Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17-20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague-Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor alpha1, alpha4, and delta subunits in the cerebral cortex of the PAE sensitive Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits' expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor alpha1, alpha4, and delta subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE did not alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor alpha4 and delta subunits' expressions in the F2 generation, and had a tendency to decrease alpha1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

  • Background: Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Trans-generationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. Methods: Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation-hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. Results: EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. Conclusions: Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation-hypnosis across 2 generations. © 2016 Research Society on Alcoholism.

  • Gestational alcohol use is well documented as detrimental to both maternal and fetal health, producing an increase in offspring's tendency for alcoholism, as well as in behavioral and neuropsychological disorders. In both rodents and in humans, parental care can influence the development of offspring physiology and behavior. Animal studies that have investigated gestational alcohol use on parental care and/or their interaction mostly employ heavy alcohol use and single strains. This study aimed at investigating the effects of low gestational ethanol dose on parental behavior and its transgenerational transmission, with comparison between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE) progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17-20 via gavage, or remained untreated in their home cages. At maturity, F1 female offspring were mated with males of the same strain and treatment and were left undisturbed through gestation. Maternal behavior was scored in both generations during the first six postnatal days. Arch-back nursing (ABN) was categorized as: 1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD showed greater amounts of ABN than LE dams and spent more time in contact with their pups. In the F0 generation, water and ethanol gavage increased ABN1 and contact with pups in SD, behaviors which decreased in treated LE. For ABN2, ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect of treatment on LE animals. In the F1 generation, prenatal exposure affected retrieval. Transgenerational transmission of LG was observed only in the untreated LE group. Strain-specific differences in maternal behavior were also observed. This study provides evidence that gestational gavage can influence maternal behavior in a strain-specific manner. Our results also suggest that the experimental procedure during gestation and genetic variations between strains may play an important role in the behavioral effects of prenatal manipulations. Copyright © 2015 Elsevier Inc. All rights reserved.

Last update from database: 3/13/26, 4:15 PM (UTC)

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