Changes in Blood Alcohol Levels as a Function of Alcohol Concentration and Repeated Alcohol Exposure in Adult Female Rats: Potential Risk Factors for Alcohol-Induced Fetal Brain Injury

Fetal alcohol syndrome and alcohol-related birth defects are the result of heavy maternal alcohol consumption during gestation. The magnitude of deficit manifested by the offspring is invariably a consequence of several risk factors that may result in high peak blood alcohol concentrations (BACs), such as the duration, timing, or pattern of alcohol consumption. In addition, the alcohol content of the consumed beverage may play a role in determining offspring developmental consequences. Because higher BACs are positively correlated with risk and severity of brain injury early in postnatal lie, initially it was important to determine how BAC is influenced by alcohol concentration and whether that influence is constant over repeated alcohol treatments. Groups of female Sprague-Dawley rats received daily intragastric intubations of 5 g/kg alcohol in one of several concentrations: 45% (v/v), 30% (v/v), 22.5% (v/v), or 15% (v/v) for a duration of 18 consecutive days. Blood samples were taken at various times postintubation on days 3,8,13, and 18 of treatment, and analyzed by headspace gas chromatography. Multivariate analyses of peak BAC, average BAC, and time to reach peak BAC revealed some noteworthy results. First, peak BAC and average BAC were significantly lower in the 45% group, compared with the other concentration groups, whereas this group also took a longer time to reach peak BAC than the other three groups. Second, peak BAC and averege BAC were higher on the last day of treatment than any of the other treatment days. These results suggest that alcohol concentration and repeated alcohol exposure can influence BAC and, as such, are important risk factors to be considered in the appraisal of alcohol-induced fetal brain injuries.     

Repeated light-dark phase shifts modulate voluntary ethanol intake in male and female high alcohol-drinking (HAD1) rats

BACKGROUND: Chronic disruption of sleep and other circadian biological rhythms, such as occurs in shift work or in frequent transmeridian travel, appears to represent a significant source of allostatic load, leading to the emergence of stress-related physical and psychological illness. Recent animal experiments have shown that these negative health effects may be effectively modeled by exposure to repeated phase shifts of the daily light-dark (LD) cycle. As chronobiological disturbances are thought to promote relapse in abstinent alcoholics, and may also be associated with increased risk of subsequent alcohol abuse in nonalcoholic populations, the present experiment was designed to examine the effects of repeated LD phase shifts on voluntary ethanol intake in rats. A selectively bred, high alcohol-drinking (HAD1) rat line was utilized to increase the likelihood of excessive alcoholic-like drinking. METHODS: Male and female rats of the selectively bred HAD1 rat line were maintained individually under a LD 12:12 cycle with both ethanol (10% v/v) and water available continuously. Animals in the experimental group were subjected to repeated 6-hour LD phase advances at 3 to 4 week intervals, while control rats were maintained under a stable LD cycle throughout the study. Contact-sensing drinkometers were used to monitor circadian lick patterns, and ethanol and water intakes were recorded weekly. RESULTS: Control males showed progressively increasing ethanol intake and ethanol preference over the course of the study, but males exposed to chronic LD phase shifts exhibited gradual decreases in ethanol drinking. In contrast, control females displayed decreasing ethanol intake and ethanol preference over the course of the experiment, while females exposed to experimental LD phase shifts exhibited a slight increase in ethanol drinking. CONCLUSIONS: Chronic circadian desynchrony induced by repeated LD phase shifts resulted in sex-specific modulation of voluntary ethanol intake, reducing ethanol intake in males while slightly increasing intake in females. While partially contrary to initial predictions, these results are consistent with extensive prior research showing that chronic stress may either increase or decrease ethanol intake, depending on strain, sex, stressor type, and experimental history. Thus, repeated LD phase shifts may provide a novel chronobiological model for the analysis of stress effects on alcohol intake.     

A Small Dose of Morphine Leads Rats to Drink More Alcohol and Achieve Higher Blood Alcohol Concentrations

Male Sprague-Dawley rats were maintained on a daily regimen of 22 hr of fluid deprivation followed by a 2-hr opportunity to take a sweetened alcoholic beverage and water for over 6 months. Durinc the week before the formal procedures of the experiment describee herein, access to the alcoholic beverage was limited to 1.5 hr, but access to water was still for 2 hr. Intakes of ethanol, in terms of g/kg, were tabulated at 30 min for half of the rats and at 90 min for the rest. On the day of formal procedures, half of the rats of the 30- and 90-min measures were given 1 mg/kg of morphine sulfate just before the drinking session, whereas the rest received physiological saline Morphine increased mean g/kg intakes of ethanol, as compared with controls, at 30 and 90 min. Blood alcohol levels were also increased These data suggest that the well-documented ability of small doses of morphine to increase rats' intake of ethanol is probably not related to its ability to produce gastrointestinal effects, but rather due to its ability to modulate central motivational mechanisms associated with ingestion.     

Effect of Calcitonin on the Alcohol Drinking of Rats

Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of Blood Alcohol Concentrations After Beer and Whiskey

To determine whether blood alcohol concentrations achieved by ingestion of various alcoholic beverages differ as a function of prandial state, healthy male volunteers, aged 24 to 48 years, were given the same amount of alcohol (0.3 g/kg) as different beverages. The alcohol was consumed in three prandial states: postprandial (1 hr after a meal, n = 10), prandial (during the meal, n = 10), and preprandial (after an overnight fast, n = 9). Each subject was tested with both beer and whiskey, and in the postprandial state also with wine and sherry, in a within-subjects design. Blood alcohol concentrations were estimated by breath analysis for 4 hr or until concentrations reached zero. Peak blood alcohol levels were higher with beer than with whiskey in the postprandial and prandial conditions ( p < 0.01), whereas the opposite was true in the preprandial state ( p < 0.05). Similarly, the area under the blood alcohol curve was higher with beer in the prandial state ( p < 0.05), and higher with whiskey in the preprandial condition ( p < 0.01). Wine and sherry yielded peak concentrations intermediate between those of beer and whiskey in the postprandial state. The results indicate that a dilute alcoholic drink can yield either higher or lower blood alcohol levels than a concentrated beverage, depending on the prandial state.     

Field and Laboratory Alcohol Detection With 2 Types of Transdermal Devices

Background: Two types of transdermal electrochemical sensors that detect alcohol at the skin surface were evaluated. One, the AMS SCRAM? device, is locked onto the ankle and is based on a fuel cell sensor; the other, a Giner WrisTAS? device, worn on the wrist, is based on a proton exchange membrane. SCRAM is used by several court systems in the United States to monitor alcohol offenders, WrisTAS, a research prototype, is not commercially available. Methods: The 2 devices were worn concurrently by 22 paid research subjects (15 men, 7 women), for a combined total of 96 weeks. Subjects participated in both laboratory‐dosed drinking to a target of 0.08 g/dl blood alcohol concentration (BAC), and normal drinking on their own; all subjects were trained to use and carry a portable fuel‐cell breath tester for BAC determinations. Overall 271 drinking episodes with BAC ≥ 0.02 g/dl formed the signal for detection—60 from laboratory dosing, and 211 from self‐dosed drinking, with BAC ranging from 0.02 to 0.230 g/dl (mean 0.077 g/dl). Results: False negatives were defined as a transdermal alcohol concentration response equivalent <0.02 g/dl when BAC ≥ 0.02 g/dl. The overall true‐positive hit rate detected by WrisTAS was 24%. The low detection rate was due to erratic output and not recording during nearly 67% of all episodes; reportedly a chipset, not a sensor problem. SCRAM correctly detected 57% across all BAC events, with another 22% (total 79%) detected, but as <0.02 g/dl. When subjects dosed themselves to BAC ≥ 0.08 g/dl, SCRAM correctly detected 88% of these events. SCRAM devices lost accuracy over time likely due to water accumulation in the sensor housing. Neither unit had false‐positive problems when true BAC was <0.02 g/dl. Conclusions: Each device had peculiarities that reduced performance, but both types are able to detect alcohol at the skin surface. With product improvements, transdermal sensing may become a valuable way to monitor the alcohol consumption of those who should be abstaining.     

Differences in Free-Choice Ethanol Acceptance between Taste Aversion-Prone and Taste Aversion-Resistant Rats

Taste aversion (TA)-prone (TAP) and TA-resistant (TAR) rats were tested for naive, nonforced acceptance of ethanol. Ethanol acceptance had played no role in line development. Rather, the lines had been developed via bidirectional, nonsibling matings based on susceptibility to develop cyclophosphamide-induced conditioned TAs to a 0.1% saccharin solution (at cyclophosphamide doses of 12.5 mg/kg for males and 15.0 mg/kg for females, ip). Rats from the 23rd selectively bred generations, with no prior exposure to ethanol, were given 24-hr access to a two-bottle choice between plain tap water and a solution of ethanol in water. Rats were initially given access to 1% ethanol in water, and the ethanol concentration was increased by 1% every 3 days to a maximum of 10%. Ethanol consumption (g ethanol consumed/kg body weight) and preference scores (volume ethanol solution consumed/total fluid intake) were determined by daily bottle weighings. At 1% ethanol concentration, there were no differences between the rat lines in terms of ethanol consumption or preference. At concentrations of 2 to 10%, TAP rats consumed less ethanol and showed a decreased preference for the ethanol solutions than TAR rats. Maximum ethanol consumption was reached at the 6% concentration for both lines. The mean (±SE) values of consumption at 6% ethanol were 1.8 (±0.8) and 5.6 (±0.5) g of ethanol/kg body weight for TAP and TAR rats, respectively. Mean (±SE) preference scores at 6% ethanol were 26 (±12) and 76 (±6) for TAP and TAR rats, respectively. These findings indicate that differences in TA conditionability may be associated with the propensity of rats to be high or low consumers of ethanol. Based on these data, it is hypothesized that high susceptibility for TA conditionability may deter many individuals from consuming the high levels of ethanol that usually precede alcohol tolerance and dependence.