Biomedical subjects

C L Randall

Publications and source records attributed to C L Randall.

101 records · Page 6Linked to original sources

PubMedDate not supplied

Effect of acute ethanol and cocaine administration on gestation days 14-17 in mice.

The teratogenic effects of the coadministration of alcohol and cocaine on gestation days 14-17 were investigated using an acute exposure model. Pregnant C57BL/6J mice were assigned randomly to treatment groups generated from a 2 (0 or 6 g/kg alcohol) x 2 (0 or 60 mg/kg cocaine) x 4 (day of treatment) factorial design. An untreated control group was also employed. On GD14, 15, 16, or 17, females were intubated with alcohol or an isocaloric solution and injected (SC) 10 min later with cocaine or saline. Litters were evaluated on GD19 following cesarean delivery. A significant number of females in the alcohol-only group treated on GD16 or GD17 delivered litters prior to GD19. The results indicated that, in general, prenatal alcohol exposure was associated with decreased fetal body weight and suggested a possible increase in malformations of vascular origin. Cocaine and the alcohol/cocaine interaction did not affect the outcome variables in any reliable manner. Thus, with the animal model employed, cocaine did not exert teratogenic effects on its own nor did it influence alcohol-induced teratogenesis.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Cocaine does not influence the teratogenic effects of acute ethanol in mice.

The teratogenic effects of the coadministration of alcohol (ethanol) and cocaine to pregnant C57BL/6J mice were investigated using an acute treatment model on gestation day 10 (GD10). The day of mating was designated as GD1. Pregnant mice were assigned to treatment groups generated from a 3(0, 4, 6 g/kg alcohol) x 3 (0, 40, 60 mg/kg cocaine) factorial design to explore possible interactive effects of these commonly abused drugs. Females were treated on GD10 (alcohol gavage followed by SC cocaine injection) and their litters were evaluated on GD19 by cesarean delivery. Two additional free-fed groups, as well as a pair-fed group, were employed. Food and water intake was recorded in treated groups. Results indicated that only the high dose alcohol produced a significant decrease in fetal body weight and a significant elevation of the incidence of kidney and limb malformations. These effects could not be attributed to restricted food intake. Cocaine was not found to produce any significant perturbations of development, either alone or in combination with alcohol. These results suggest that acute prenatal cocaine exposure on GD10 does not produce teratogenic effects when administered alone or in combination with acute alcohol in C57BL/6J mice, at least under the present experimental conditions.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Effect of prenatal ethanol exposure on response to abrupt reward reduction.

The purpose of this study was to examine the effects of prenatal ethanol exposure on an appetitively-motivated behavioral task (consummatory negative contrast) that involves quantification of an animal's response to an abrupt, unexpected reduction in reward (sucrose solutions). Pregnant Long-Evans rats received isocaloric liquid diets containing either 35% or 0% ethanol-derived calories on days 6-20 of gestation. A pair-feeding procedure was employed, and a lab chow control group also was included. Adult male offspring from these three prenatal treatment groups were used for behavioral testing. Results indicated all groups exhibited suppressed responding subsequent to reward reduction. This effect gradually diminished in all prenatal treatment groups over several test sessions. While there was a numerical tendency for ethanol-exposed offspring to exhibit a smaller initial contrast effect (less response inhibition) and recover to control levels at a faster rate than the sucrose and lab chow control groups, this effect was not statistically significant. Thus, prenatal ethanol exposure does not appear to greatly influence the response to abrupt, partial reward reduction in adult rat offspring.

Animals↗

PubMedDate not supplied

Prenatal ethanol exposure in C57 mice: effects on pregnancy and offspring development.

Pregnant mice were fed lab chow or isocaloric liquid diets containing different concentrations of ethanol or sucrose from Day 5 through Day 17 of gestation. Ethanol added to the diet reduced ad lib consumption compared to that of the diet with sucrose. The reduced consumption was accompanied by an attenuated weight gain during pregnancy. The attenuated weight gain, however, was not specific to alcohol as evidenced by an equivalent attenuation for sucrose controls pair-fed to the ethanol group. Prenatal ethanol exposure increased neonatal mortality which appeared to be unrelated to the prenatal attenuated weight gain or to postnatal nurturance. Surviving offspring, reared by their biological mothers, had body weights similar to controls at birth and during lactation. However, in contrast to previous reports, mice prenatally exposed to ethanol manifested weight reductions near weaning that extended into adulthood (60 days). In spite of the increased mortality and reduced body weight, motor activity assessed by either longitudinal or cross-sectional methods was not influenced by the treatments. Possible mechanisms for the delayed weight reduction include retarded maturation and/or dysfunction of neural systems involving food regulation.

Animals↗

PubMedDate not supplied

Acute gestational cocaine exposure alone or in combination with low-dose ethanol does not influence prenatal mortality or fetal weight in mice.

The teratogenic effects of cocaine and ethanol were investigated using an acute treatment model of C57BL/6J mice treated on gestation day 15 (GD15) with evaluation on GD17. Females were intubated once with a subteratogenic dose of ethanol (0 or 4 g/kg) and injected subcutaneously twice, 1 h apart, with equal doses of cocaine HCl (0 or 60 mg/kg), for a final daily dose of 120 mg/kg. The first cocaine injection followed ethanol by 10 min. Blood ethanol levels (BEL) and plasma cocaine levels were determined, and pair-feeding was employed. The results revealed no group differences on pregnancy outcome. That is, maternal weight gain, total number of implants, prenatal mortality, and fetal body weight were not statistically different. No significant differences in BEL or plasma cocaine levels were found among the various treatment groups. These results suggest that, under these conditions, relatively high levels of cocaine (120 mg/kg, SC), given alone or in combination with subteratogenic doses of ethanol late in pregnancy, are not teratogenic in mice.

Animals↗

PubMedDate not supplied

Cognitive behavioral therapy delays relapse in female socially phobic alcoholics.

The present study was conducted to test the hypothesis that socially phobic alcoholics treated with Cognitive Behavioral therapy (CBT) will have better drinking outcomes than those treated with Twelve-Step Facilitation therapy (TSF). Three hundred ninety-seven treatment-seeking alcoholics with concurrent social phobia were compared retrospectively to a matched sample of 397 alcoholics without social phobia. Treatment was delivered in an outpatient setting, and patients were randomized to either CBT, TSF, or Motivational Enhancement therapy (MET). The groups were compared on self-reported drinking measures (e.g., quantity and frequency of drinking, and time-to-event measures) during treatment period and monthly for 1 year following treatment. Survival analyses revealed that female outpatients with social phobia showed delayed relapse to drinking when treated with CBT rather than TSF; the reverse was true for female outpatients without social phobia. Survival analyses in male outpatients with and without social phobia revealed an opposite trend, though it was not statistically significant. These data suggest that Cognitive Behavioral therapy is superior to Twelve-Step Facilitation therapy for the treatment of alcohol problems in specific populations. namely socially phobic women seeking outpatient treatment.

Adult↗

PubMedDate not supplied

Alcohol plus cocaine prenatally is more deleterious than either drug alone.

A C57BL/6J mouse model was used to examine the coteratology of alcohol and cocaine. Plugged female mice were assigned to one of four treatment groups: control, cocaine only, alcohol only, or alcohol-cocaine. Experimental animals were treated from gestation day (GD) 6-18 and were killed the morning of GD 19. Alcohol was administered in a liquid diet containing 25% ethanol-derived calories (25% EDC), and cocaine was administered daily in subcutaneous injections of 60 mg/kg. All groups were pair-fed to the alcohol-cocaine group. The results showed that the cocaine-only and the alcohol-cocaine group had fewer successful pregnancies. The alcohol-only group had the lowest maternal weight gain from GD 1-19. There were no treatment group effects on litter size, sex ratio, or prenatal mortality. Importantly, fetuses in the alcohol-cocaine group weighed less than all other groups and had the greatest occurrence of fetal anomalies. These data confirm the teratogenic effects of alcohol and cocaine and suggest that the combination of the two drugs, if administered chronically, is more deleterious to pregnancy and fetal outcome than either drug alone.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Aspirin reduces alcohol-induced prenatal mortality and malformations in mice.

Oral alcohol administration (5.8 g/kg) on gestation day 10 resulted in an increase in both prenatal mortality and birth defects as well as decreased fetal weight in C57BL/6J mice. Aspirin pretreatment (150 mg/kg subcutaneously) significantly reduced the number of malformed pups and prevented the increase in prenatal mortality produced by alcohol. The mechanism of action remains to be elucidated.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Executive turnover.

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Data Collection↗

PubMedDate not supplied

Effect of prenatal ethanol exposure on activity and shuttle avoidance behavior in adult C57 mice.

Although the morphological teratogenic actions of ethanol have been well established in mice, studies on the behavioral teratogenic effects of alcohol have been primarily conducted with rats. The purpose of this study was to examine the behavioral effects of prenatal alcohol exposure in C57 mice, a strain known to be highly sensitive to the teratogenic actions of ethanol. Pregnant mice were administered a liquid diet containing 25% ethanol-derived calories (EDC) from day 5 through day 18 of gestation. Control animals were pair-fed an isocaloric 0% EDC diet during the same period of time, with sucrose substituted for ethanol. At 23 days of age, offspring were tested for spontaneous locomotor activity in an open field. At 70 days of age, different offspring were tested in a shuttle-avoidance task. The results demonstrated that the 25% EDC progeny were more active than controls. In addition, prenatal alcohol exposure produced a deficit in acquisition and performance of a shuttle-avoidance task. Alcohol-treated offspring made fewer avoidance responses and required more trials to reach a criterion performance of 10/10 avoidances consecutively followed by at least 9/10 avoidances. These results importantly contribute to the development of an animal model of Fetal Alcohol Syndrome in which both the behavioral and morphological consequences of prenatal alcohol exposure may be assessed in the same species.

Animals↗

PubMedDate not supplied

Effects of acute alcohol exposure during selected days of gestation in C3H mice.

This investigation was designed to evaluate the teratogenic potential of a single alcohol exposure on one of nine specific days of gestation using a mouse model. C3H mice were intubated with alcohol on either Day 7, 8, 9, 10, 11, 12, 14, 16, or 18 of pregnancy in a dose of 0.0, 2.5, or 5.0 g/kg. On day 19 of gestation, the fetuses were removed by caesarian section, weighted, and fixed in Bouin's solution for subsequent free-hand sectioning. The results demonstrated that (1) acute prenatal alcohol exposure tended to decrease fetal body weight as the dose of alcohol increased, an effect that was most pronounced following exposure on Day 18 of gestation, and (2) neither the dose of alcohol nor the day of acute exposure significantly influenced implantations, resorptions, dead fetuses, or the incidence of fetal malformations across groups.

Abnormalities, Drug-Induced↗