Edward P. Riley

Deficits on a spatial navigation task following prenatal exposure to ethanol.

Performance on a Morris water task was examined in young rats whose mothers consumed a liquid diet consisting of 35% ethanol-derived calories (EDC) during pregnancy. Offspring of pair-fed (0% EDC) and ad lib lab chow (LC) dams served as controls. Rats were required to find a platform submerged below the surface in a pool of opaque water. A trial ended when the rat remained on the platform for 15 sec, or had been in the tank for 180 sec without reaching the platform. Subjects received 5 trials daily for 3 consecutive days, followed by reversal training on Day 4. Groups did not differ in swimming ability. On Day 1 there were no group differences among females in latency to reach the platform or in distance traveled, but male 35% EDC and 0% EDC animals had shorter latencies than LC controls. On Day 2, latencies and distance traveled of LC and 0% EDC controls decreased while 35% EDC animals showed no change from Day 1, so that alcohol-exposed rats took longer to reach the platform and traveled a greater distance than controls. On Day 3, 35% EDC females took longer than controls to reach the platform, and 35% EDC animals of both sexes traveled a greater distance than controls. Search patterns on the first reversal trial on Day 4 suggest the differences are in spatial processing and not learning per se, but more so in alcohol-exposed males than females. The impaired performance on this task suggests that prenatal alcohol exposure alters the ability to process spatial information.

Neonatal ethanol exposure: functional alterations associated with cerebellar growth retardation.

The effects of alcohol exposure during the brain growth spurt on development and on behavioral assessments of functional alterations in the cerebellum were examined in the rat. Rat pups were exposed via an artificial rearing technique to either a 2.50% w/v or 2.15% w/v EtOH-milk formula during a period encompassing the brain growth spurt. An artificially reared control group and a suckle control group were also included. Peak blood alcohol concentrations for animals in the high and low dose alcohol exposure groups were approximately 300 mg/dl and 180 mg/dl, respectively. Reductions in brain minus cerebellum to body weight (BR-C/BD) and cerebellum to body weight (C/BD) ratios were noted in animals from each of the alcohol-treated groups. Some catch-up growth in terms of brain mass was noted in animals from each of the alcohol-exposed groups. Animals exposed to alcohol during the neonatal period displayed deficits on several tests of balance and motor ability. Alcohol-exposed animals performed more poorly than controls when traversing two parallel horizontal rods and on tests of hindlimb and head elevation. No differences were noted in the ability to remain on a rotating drum. These results suggest that some of the behavioral consequences of neonatal ethanol exposure might be due to ethanols actions on the cerebellum.

Amphetamine-induced activity after fetal alcohol exposure and undernutrition in rats

Behavioral responses to amphetamine were examined in 28- and 42-day-old rats whose mothers consumed a liquid diet consisting of 35% ethanol-derived calories (EDC) during pregnancy. Offspring of pair-fed (0% EDC) and ad lib chow (LC) dams were included as controls. Animals received 0.0, 0.5, 1.0, or 2.0 mg/kg/ml d-amphetamine prior to single 2-hr tests in automated activity monitors. At 28 days of age, when there were no differences in activity after saline injection, 35% EDC males were more active (measured by distance traveled) than LC and 0% EDC males following treatment with 2.0 mg/kg amphetamine. Thirty-five percent EDC females exhibited brief reductions in activity relative to LC females but were not different from 0% EDC females at 28 days of age following 2.0 mg/kg amphetamine. When treated with 1.0 mg/kg amphetamine, 28-day-old 0% EDC males were less active than LC and 35% EDC males, who did not differ from each other at this dose. At 42 days of age, animals from both liquid diet groups were less active than LC controls following 2 mg/kg amphetamine. These results suggest that both prenatal alcohol exposure and undernutrition may influence the postnatal functional status of catecholamine systems but that the nature of those functional changes varies with type of prenatal insult, sex and age of the animal at testing.

Fetal alcohol effects in long- and short-sleep mice: activity, passive avoidance, and in utero ethanol levels

Genetic differences in susceptibility to fetal alcohol effects (FAE) have been suggested by both human and animal studies. The Long-Sleep (LS) and Short-Sleep (SS) mouse lines, selectively bred for differences in ethanol-induced narcosis, provide a model for studying differential alcohol sensitivity in the etiology of FAE. LS and SS mice were intubated with either 2.9 g/kg (20% w/v) ethanol (E) or an isocaloric amount of sucrose (S) twice per day (6 hr apart) on Days 7 through 15 of pregnancy. An untreated control group (C) was maintained for each line. Offspring were fostered to lactating Rockland-Swiss mice at birth. LS offspring prenatally exposed to ethanol exhibited increased open-field activity relative to LS controls, but this effect was due to the overactivity of one litter. Activity for SS mice prenatally exposed to ethanol did not differ from control levels. Ethanol content in blood (280 mg/dl), amniotic fluid (258 mg/dl), and fetal tissue (230 mg/dl) did not differ in similarly treated LS and SS dams. In a second experiment, females were treated from Days 7 through 18 of gestation, and their offspring were tested for either open-field activity or passive avoidance learning. There were no group differences in open-field activity, but LS mice prenatally exposed to alcohol took more trials to reach a passive avoidance criterion than their controls, whereas similarly treated SS mice did not differ from controls. These results suggest that genetically-mediated sensitivity to ethanol influences susceptibility to FAE and that this may be task specific.

Apomorphine-induced motor behavior in rats exposed prenatally to alcohol☆

We psychopharmacologically examined dopamine function in rats exposed to ethanol prenatally. Pregnant rats received liquid diets of 35% or 0% ethanol-derived calories (EDC), or ad lib lab chow (LC). Twenty-eight-day-old offspring received systemic doses of apomorphine chosen to stimulate predominantly presynaptic (0.02 or 0.1 mg/kg) or postsynaptic dopamine receptors (2.0 or 5.0 mg/kg). Behavior was scored automatically for 60 min in an open field. For males, prenatal ethanol exposure resulted in a dose-response shift to the left for locomotor activity. Females exposed to the liquid diet, with or without ethanol, showed less of an increase in locomotor activity following the 5.0 mg/kg dose of apomorphine than did LC controls. There were no effects of prenatal treatment on repetitious motor behavior in the automated open field or on stereotypy scored by direct observation in separate groups of rats. The results are consistent with an hypothesis that prenatal ethanol exposure alters the sensitivity of postsynaptic (perhaps mesolimbic) dopamine systems important to locomotor activity in young male rats.

Ethanol teratogenesis in mice selected for differences in alcohol sensitivity

Long-Sleep (LS) and Short-Sleep (SS) mice, selectively bred for differences in ethanol-induced narcosis, were administered ethanol (2.9, 4.0, 4.5, or 5.0 g/kg) twice per day during the period of organogenesis. On gestation day 18, the dams were sacrificed and the uterine horns were examined for live, dead, and resorbed fetuses. Live fetuses were weighed and assessed for either skeletal or soft tissue anomalies. The 5.8 g/kg/day dose had no effect on prenatal mortality, litter size, body weight, or number of physical anomalies in either line. However, the alcohol-sensitive LS mice exposed to ethanol doses of 8.0 g/kg/day or more evidenced decreased body weights while weights for the alcohol-insensitive SS mice differed from controls at only the highest dose tested. The incidence of skeletal variants was increased in the LS mice exposed to the 10 g/kg/day ethanol dose. These results indicate genetically-mediated alcohol sensitivity increases susceptibility to some of the fetotoxic effects of in utero alcohol exposure.

Altered grooming responses to stress in rats exposed prenatally to ethanol

The effects of prenatal alcohol exposure on grooming, locomotion, and rearing in response to stress were examined in adult rats whose mothers consumed a liquid diet containing 35% ethanol-derived calories (EDC). Offspring of both pair-fed 0% EDC mothers and ad libitum chow-fed mothers were included as controls. In Experiment 1, females groomed more than males following placement into a novel test chamber, but no differences due to prenatal treatment were observed. Ethanol-exposed animals groomed more than controls following the stress of a forced 1-min swim (Experiment 2), but when rats tested in Experiment 1 were observed again after forced swim stress (Experiment 3), no differences due to prenatal treatment or sex were observed. Experiment 4 examined the effects of pretreatment with 1 mg/kg naloxone on novelty-induced grooming and as in Experiment 1 prenatal treatment did not affect grooming responses. Females again groomed significantly more than males and naloxone reduced grooming equally for all groups. The results suggest that novelty-induced grooming is a sex-influenced behavior, with females grooming more than males, and that animals exposed prenatally to alcohol and tested as adults may have altered responses to certain stressors (i.e., forced swim) under specific conditions. The altered grooming response of alcohol-exposed rats to swim stress can be eliminated by preexposing them to novelty stress.

Fixed-ratio performance and subsequent extinction in rats prenatally exposed to ethanol

Pregnant Long-Evan rats were fed isocaloric liquid diets containing 35%, 23%, 11%, or 0% ethanol-derived calories (EDC) from Day 5 to Day 20 of gestation. Shortly after weaning, male offspring of these mothers were tested for the acquisition and extinction of a fixed-ratio (FR) barpress response. As the schedule requirement was progressively increased from FR 2 to FR 33, the 35% (EDC) offspring consistently had the lowest response rates, 23% and 11% (EDC) offspring were intermediate, and the 0% (EDC) progeny had the highest response rates (p <.01). During extinction, this pattern was reversed; the number of responses increased as a function of prenatal alcohol exposure (p <.025).

Responses to ethanol challenge in long- and short-sleep mice prenatally exposed to alcohol.

Individual sensitivity to alcohol may influence the severity of functional deficits due to prenatal alcohol exposure. To examine this hypothesis, Long-Sleep (LS) and Short-Sleep (SS) mice, selectively bred for differences in ethanol-induced narcosis, were intubated with either 2.9 g/kg ethanol (E) or an isocaloric amount of sucrose (S) twice per day on days 7 through 15 of pregnancy. An untreated control group (C) was maintained for each line. Offspring were fostered to lactating Rockland-Swiss mice at birth. Males and females from each litter were challenged with an acute dose of ethanol (3.8 g/kg) at 30 days of age. Measures of sleep time duration, waking blood ethanol concentrations (BEC), rectal temperatures, heart rate, and ethanol clearance were obtained to examine whether the acute effects of ethanol are altered by prenatal alcohol exposure. Prenatal alcohol exposure did not differentially affect responses to ethanol challenge within either genotype. Ethanol-induced hypothermia, heart-rate depression, and sleep time did differ between genotypes, with LS more affected than SS mice. Ethanol clearance rates were faster for SS than LS mice. These results suggest postnatal pharmacological responses to acute ethanol challenge are not altered by prenatal alcohol exposure in LS and SS mice. Prenatal alcohol-exposed offspring of both mouse genotypes showed lower average heart rate responses than controls, suggesting this measure may be a sensitive indicator of prenatal alcohol effects in mice.

Absence of differential motoric and thermic responses to clonidine in young rats exposed prenatally to alcohol

We studied the involvement of altered noradrenergic function in the behavioral consequences of fetal ethanol exposure. Pregnant rats were fed a liquid diet containing 35% Ethanol-Derived Calories (EDC), pair-fed a 0% EDC diet with sucrose substituted isocalorically for ethanol, or fed ad lib lab chow. In Experiment 1, offspring from these prenatal treatment groups were injected with the alpha-adrenergic agonist clonidine (0.5 or 2.0 mg/kg) at 10 or 42 days of age and showed age-characteristic, dose-dependent increases in locomotor activity, exploration, forelimb treading, and catalepsy. In Experiment 2, offspring were injected with clonidine (0.25 or 1.0 mg/kg) at 10, 14, or 18 days of age, and locomotor activity and wall-climbing were observed in a warm chamber (33 degrees C). Catalepsy and rectal temperature were also scored. There were no significant differential effects of clonidine on any prenatal treatment group at any age for any measure of activity or rectal temperature. The results do not support the hypothesis that fetal ethanol exposure alters noradrenergic systems in behaviorally significant ways.