Acute sensitivity and acute tolerance to ethanol in preweanling rats with or without prenatal experience with the drug

Abstract

The present study examined behavioral sensitivity and acute tolerance to ethanol in infants with or without a moderate prenatal ethanol experience. During gestational days 17-20 dams received 0.0 or 2.0 g/kg ethanol. On postnatal day 13 pups were administered 0.0, 0.5 or 2.5 g/kg ethanol prior to assessment of locomotion. One third of the pups were evaluated at 5-10, 30-35 and 60-65 min after ethanol administration; another third was tested only during the last two post-administration periods; and the remaining third was tested only at 60-65 min. At 30-35 min blood ethanol levels were similar to those attained at 60-65 min. The main results of the study were: (a) The 2.5 g/kg ethanol dose induced biphasic motor effects: stimulation 5-10 min after drug administration and sedation after 30-35 or 60-65 min. (b) Infants exhibited acute tolerance to ethanol's sedative effects. (c) Although pups prenatally treated with ethanol exhibited heightened locomotor activity levels, acute sensitivity and tolerance were not affected by prenatal treatment. In summary, infants are sensitive to biphasic motor consequences of ethanol and readily exhibit acute tolerance to ethanol's sedative effects. In addition, moderate prenatal ethanol exposure was sufficient to induce hyper-reactivity in the offspring without affecting habituation.

Figure 1

Blood ethanol concentration (mg %) as a function of prenatal (0.0 or 2.0 g/kg) and postnatal (0.5 or 2.5 g/kg) ethanol treatments, and post-administration time (7.5, 32.5 or 62.5 min). Vertical lines illustrate standard errors of the means.

Figure 2

Prenatal (0.0 or 2.0 g/kg) and postnatal (0.0, 0.5 or 2.5 g/kg) ethanol treatments and testing conditions that define the design under consideration. Given the structure of the design we will refer to it as “inverted ladder”. One third of the animals corresponding to each prenatal treatment were sequentially evaluated at 5–10, 30–35 and 60–65 min [group early-intermediate-late (E–I–L)]. Another third were tested only during the last two post-administration periods [30–35 and 60–65 min; group intermediate-late (I-L)] while the remaining subjects were tested only at post-administration time 60–65 min. [group late (L)].

Figure 3

Figure 3a and 3b: Overall behavioral profiles as a function of prenatal (0.0 or 2.0 g/kg) and postnatal (0.0, 0.5 or 2.5 g/kg) ethanol treatments, and testing conditions [early-intermediate-late (E–I–L), intermediate-late (I-L) or late (L)]. Group E–I–L was evaluated at 5–10, 30–35 and 60–65, while group I-L was evaluated at 30–35 and 60–65 min. Finally, group L was tested at 60–65 min. Vertical lines illustrate standard errors of the means.

Figure 3

Figure 3a and 3b: Overall behavioral profiles as a function of prenatal (0.0 or 2.0 g/kg) and postnatal (0.0, 0.5 or 2.5 g/kg) ethanol treatments, and testing conditions [early-intermediate-late (E–I–L), intermediate-late (I-L) or late (L)]. Group E–I–L was evaluated at 5–10, 30–35 and 60–65, while group I-L was evaluated at 30–35 and 60–65 min. Finally, group L was tested at 60–65 min. Vertical lines illustrate standard errors of the means.

Figure 4

Locomotor activity as a function of prenatal (0.0 or 2.0 g/kg) and postnatal (0.0, 0.5 or 2.5 g/kg) ethanol treatments in pups from group early-intermediate-late (E–I–L). Data are collapsed across minutes and post-administration interval. The ANOVA revealed a significant effect of prenatal ethanol treatment. Vertical lines illustrate standard errors of the means.

Figure 5

Locomotor activity as a function of postnatal ethanol administration (0.5 or 2.5 g/kg) and post-administration interval (5–10, 30–35 and 60–65). In this figure we included only data from group E–I–L. Data are collapsed across minutes and prenatal ethanol treatment. The ANOVA revealed a significant interaction between postnatal ethanol treatment and post-administration time. Vertical lines illustrate standard errors of the means.

Figure 6

Locomotor activity as a function of prenatal ethanol treatment (0.0 or 2.0 g/kg) and testing condition [early-intermediate-late (E–I–L), intermediate-late (I-L) or late (L)]. Data are collapsed across minutes and postnatal ethanol administration. The data included in this picture are from the first test of E–I–L, I-L and L groups. The ANOVA revealed a significant interaction prenatal ethanol treatment by testing condition. Vertical lines illustrate standard errors of the means.

Figure 7

Locomotor activity as a function of postnatal ethanol administration (0.5 or 2.5 g/kg) and testing condition [early-intermediate-late (E–I–L), intermediate-late (I–L) or late (L)]. The activity scores included in this figure are from the first test of E–I–L, I–L and L groups. Data are collapsed across prenatal ethanol treatment. The ANOVA revealed a significant interaction between postnatal ethanol treatment, testing condition and minutes. Vertical lines illustrate standard errors of the means.

Figure 8

Locomotor activity as a function of postnatal ethanol administration (0.5 or 2.5 g/kg) and testing condition [early-intermediate-late (E–I–L), intermediate-late (I–L) or late (L)]. In this picture has been taking into account activity data collected at 60–65 min. Data are collapsed across minute and prenatal ethanol treatment. The ANOVA revealed a significant interaction between postnatal ethanol treatment and testing condition. Vertical lines illustrate standard errors of the means.