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Biomedical subjects

F E Lancaster

Publications and source records attributed to F E Lancaster.

At least 19 recordsLinked to original sources

Dissociation between the time course of ethanol and extracellular dopamine concentrations in the nucleus accumbens after a single intraperitoneal injection.

BACKGROUND: Dopamine release in the nucleus accumbens has been linked to the reinforcing effects of ethanol, but the time course or relationship of this response to ethanol concentrations in the brain has not been studied. METHODS: Various doses of ethanol (0-2.0 g/kg) were administered intraperitoneally to male Sprague Dawley rats, and dopamine and ethanol were simultaneously analyzed in dialysate samples from the nucleus accumbens. A separate study to compare the ethanol-induced dopamine response in male and female rats was carried out by using a 1 g/kg intraperitoneal dose of ethanol. RESULTS: In male rats, 1 and 2 g/kg ethanol significantly increased dialysate dopamine by 40% over basal, whereas 0.25 and 0.5 g/kg ethanol produced a nonsignificant 20% increase. Dialysate ethanol concentrations exhibited a curvilinear decline after reaching peak levels for the lower doses but showed a linear decrease after 1 and 2 g/kg. There was a dissociation between the time courses of extracellular dopamine and ethanol after 1 and 2 g/kg ethanol treatment. The dopamine response returned to basal within 90 min, whereas the ethanol concentrations remained elevated. In a separate study that compared male and female rats, the ratio of the dopamine response over basal to the dialysate ethanol concentrations was significantly decreased at 60 min after an injection of 1 g/kg. However, there were no differences between males and females. CONCLUSIONS: The dissociation between dopamine and ethanol levels may reflect the development of acute tolerance to ethanol-induced dopamine release in the nucleus accumbens within the time course of a single acute injection. Given the strong links between dopamine and ethanol reinforcement, our findings may be relevant for understanding the time course of ethanol's reinforcing effects in vivo.

Animals↗

Determination of benzidine in the food colours tartrazine and sunset yellow FCF, by reduction and derivatization followed by high-performance liquid chromatography.

Free and bound benzidine, a non-sulphonated aromatic amine (NSAA), were determined in the food colours tartrazine and sunset yellow FCF. Bound amines were released by reducing with sodium dithionite, then total NSAAs were extracted into chloroform, transferred to aqueous acid solution and diazotized with sodium nitrite before coupling with 2-naphthol-3,6-disulphonic acid, disodium salt (R-salt). Coloured benzidine and aniline derivatives (BZDRS and ANRS) were analysed using reversed-phase ion pair high-performance liquid chromatography (HPLC) and an absorbance detector set at 548 nm. Levels of total benzidine were similar to those reported in studies conducted in the USA, and ranged from < 5 to 270 ng/g. Total aniline was also determined (0.2-188 micrograms/g). Recoveries of benzidine with this method were found to be lower than expected (average ca 46%), but were reproducible. Detection limits were 15-20 ng BZDRS/g (3-4 ng benzidine/g). Mass spectrometry (LC-MS) was evaluated for identifying and determining purity of the standards, but difficulties were encountered when the methodology was applied to commercial samples.

Aniline Compounds↗

Gender differences in blood levels, but not brain levels, of ethanol in rats.

Female rodents tend to drink more alcohol than males, a difference that emerges at puberty and appears to vary over the female estrous cycle. In addition, male and female rodents display different responses to alcohol; for example, female rats are reported to have faster elimination rates than males. We were interested in whether circulating ovarian hormones influence alcohol distribution to or elimination from the brain of rats, which might explain observed differences in drinking behavior. We administered 0.8 g/kg of ethanol via intraperitoneal injection to age-matched male and female Sprague-Dawley rats. Extracellular brain ethanol was sampled using microdialysis, and vascular ethanol concentrations were determined via tail blood collection, in two separate experiments. Ethanol pharmacokinetic parameters were calculated for both compartments. There were no differences in pharmacokinetic parameters due to gender or estrous cycle stage in brain ethanol concentration profiles. There were, however, differences in blood ethanol profiles: females showed faster elimination rates and a smaller area under the ethanol concentration versus time curve than males. In addition, the maximum concentration varied significantly across the estrous cycle. These results suggest that (1) circulating ovarian hormones do not influence alcohol distribution to the brain, but do influence distribution to more peripheral tissues such as the tail; and (2) apparent differences in tail blood alcohol levels may not reflect differences in brain levels.

Animals↗

Sex differences in voluntary drinking by Long Evans rats following early stress.

Models for early stress and voluntary drinking were used to determine the contribution of early stress to increased intake of alcoholic beverages during puberty and adulthood. Newborn litters of Long Evans rats were: (1) stressed by daily separation from the mother for 15 min/day on days 1 to 7 of life ["handled" (H)]; or (2) left untouched with the mother on days 1 to 7 of life ["nonhandled" (NH)]. All animals were weaned on day 22, separated by sex (M and F), and caged individually with an assignment of 10 animals per sex per treatment group (H and NH). From 25 to 85 days of age, all animals were given free access to beer containing 5% ethanol (v/v), water, and regular laboratory food. Beer, food, and water intake was measured daily at the same time each day, and animals were weighed weekly. HM had greater ethanol intake and preference for ethanol during the peripubertal period (days 32 to 45), compared with all other groups. There were no differences in ethanol intake between NHF and NHM. HM had greater ethanol preference than HF on 22 of the 60 drinking days. HF consumed the same amount of water as the males and significantly greater amounts of water than NHF on 28 of the 60 drinking days. HM had greater ethanol preference than NHM on 8 of the 60 drinking days. From day 75 to day 85, HF had greater ethanol intake than HM, and NHF had greater ethanol intake than NHM. There were no differences in body weights of HF and NHF throughout the study. Growth of HM lagged behind NHM into adulthood. Early stress of males was linked to increased ethanol intake during the peripubertal and adult periods and stunted body growth into adulthood. Early stress of females was linked to polydipsia (water) throughout development and continuing into adulthood, and to increased alcohol intake in adulthood.

Alcohol Drinking↗

Physical and motor development in male and female rat offspring prenatally exposed to gamma radiation.

The effects of radiation on physical and motor development of male and female rats exposed to ionizing radiation in utero were studied. Rats were exposed to three different doses of radiation (150 rad, 15 rad and 6.8 rad, considered as high, moderate and low doses of radiation respectively) on the 20th day of prenatal life. Exposure to 150 rad contributed to significantly lower body weights of both male and female rat offspring. Upper jaw tooth eruption was delayed in 150 rad treated male offspring, as well as in 15 rad and 150 rad treated female offspring. Cliff-avoidance response was delayed in 6.8 rad, 15 rad, and 150 rad treated male offspring; and 150 rad treated female offspring. Lower jaw tooth eruption, eye opening, and crawling were not affected by radiation in male or female animals. Results indicate that radiation affected the developmental parameters of both male and female rat offspring, and sex of the offspring played no role in the magnitude of radiation induced damages.

Analysis of Variance↗

High-performance liquid chromatographic separation of carminic acid, alpha- and beta-bixin, and alpha- and beta-norbixin, and the determination of carminic acid in foods.

During a study of natural food colours, a simple and reliable high-performance liquid chromatography system was developed for use with cochineal and annato. An isocratic mobile phase, consisting of methanol and 6% aqueous acetic acid, resolved bixin and norbixin, while a gradient system was used to separate carminic acid and the annato compounds. The carminic acid contents of cochineal extract, carmine and carmine hydrosoluble were determined using an isocratic mobile phase (40:60, v/v). The detection limit for carminic acid in the various products was approximately 100 ng/g. Carminic acid was determined quantitatively in fruit beverages, yogurt and candies. It was demonstrated that, because of decomposition, carminic acid was not suitable for use in candies when manufacturing temperatures above 100 degrees C were required. Most membrane filters are not suitable for use with cochineal solutions, but a cellulose membrane filter did not adsorb carminic acid and was used successfully to remove impurities from water-based cochineal products and food extracts containing carminic acid.

Carmine↗

Sex differences in alcohol preference and drinking patterns emerge during the early postpubertal period.

Young male and female Sprague-Dawley rats (30 days old) were assigned randomly to three treatment groups: (1) alcohol treatment--received beer with 5% ethanol added, food, and water ad libitum; (2) pair-fed treatment--received nonalcoholic beer plus sucrose and food to match intake by the alcohol-treated animals; and (3) control treatment--received food and water ad libitum. Animals were tested for alcohol preference for 24 hr and then received their assigned treatments for a period of 30 days, followed by a period of abstinence before alcohol preference testing again at 74 days of age. Males given free access to beer and water did not drink large quantities of beer. Females given free access to beer and water drank a lot of beer on the first day, but decreased intake until approximately 52 days of age. A developmental change in young female rats at approximately 52 days of age resulted in increased voluntary ethanol intake, possibly caused by hormonal changes associated with the establishment of estrous cycles. When the animals were tested for alcohol preference at 74 days of age after a period of abstinence, males and females in the pair-fed group had greater alcohol preference than animals in the other groups. Females in the pair-fed group had greater alcohol intake based on body weight than males in the pair-fed group and males and females in all other groups. These results provide insight into sex differences in the development of voluntary drinking behavior and responses of drinking behavior to the early stress of pair-feeding.

Age Factors↗

Alcohol and the brain: what's NO got to do with it?

A potential role for nitric oxide in alcohol-induced changes in brain function is discussed. Chronic alcohol exposure may lead to excitotoxicity partially due to increased levels of nitric oxide (NO). Excessive NO has been linked to cytotoxicity in neurons, glia and myelin. Cytokines produced in response to cell injury may trigger increased production of NO. These events may be involved in alcohol-induced brain damage. Formation of NO has recently been linked to increased preference for and tolerance to alcohol. A hypothesis for prevention and treatment of alcohol-induced brain damage, and craving and alcohol intake by alcoholics is proposed.

Brain↗

Gender differences in animal studies. Implications for the study of human alcoholism.

The reasons for gender differences in alcohol intake, responses to alcohol, and consequences of alcohol abuse in humans and in animals are poorly understood. Animal models for the study of alcoholism have been focused primarily on the study of male rodents, although researchers have observed that female rodents drink more alcohol than males and have sex-related differences in drinking patterns and responses to alcohol. In humans, the difference between the sexes is the opposite of rodents, with males drinking more than females. These results suggest differences between the sexes and differences between humans and rodents in drinking behavior and responses to alcohol which may be based on a complex interaction of social, genetic, hormonal, neurobiologic, and environmental factors. Four new studies are introduced to identify sex-distinct genetic influences in alcohol-related phenotypes, sex-based differences in behavioral responses to alcohol, sex differences in responses of brain reward systems to alcohol, and interactions of the anxiolytic effects of alcohol with steroids and the estrous cycle.

Alcohol Drinking↗

Alcohol and white matter development--a review.

This is a review of the literature on the effects of alcohol on white matter development. For many years, human and animal studies have reported the vulnerability of developing white matter to the effects of alcohol. However, until recently, studies on alcohol and white matter were limited by existing technology. New technology documenting the presence of neurotransmitter receptors and ion channels on glial cells now provides a new focus for research on alcohol and white matter development. New research using new technology should enlarge our knowledge of the role of glial cells in brain damage associated with alcohol exposure during development.

Animals↗

Gender differences in the brain: implications for the study of human alcoholism.

Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol.

Alcoholism↗

Locomotion and physical development in rats treated with ionizing radiation in utero.

Effects of ionizing radiation on the emergence of locomotor skill, and physical development were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Results indicated that relatively moderate (15 rad) to high (150 rad) doses of radiation had effects on certain locomotion and physical development parameters. Exposure to 150 rad delayed pivoting, cliff-avoidance, upper jaw tooth eruption, and decreased body weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption were marginally delayed in the 150 rad treated animals. Exposure to 15 rad delayed pivoting and cliff-avoidance.

Animals↗

Brain myelination in rats treated with ionizing radiation in utero.

Effects of ionizing radiation on brain myelination and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with three different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Exposure to 150 rad reduced body, brain, ovary, kidney, heart and spleen weights. Prenatal exposure to 150 rad of radiation reduced the cerebral cortex weight by 22 percent at 30 days of age, and 20 percent at 52 days of age which caused a reduction in cerebral cortex myelin content by 20 and 23 percent at the ages of 30 and 52 days respectively. This dose did not affect the myelin content of the cerebellum or the brain stem, or the myelin concentration (mg myelin/g brain tissue) of the cerebral cortex, cerebellum, and the brain stem. The cerebral cortex weight of the 15 rad treated rats was reduced at the age of 30 days. Exposure to 15 rad, and 6.8 rad did not affect either the myelin content or the myelin concentration of these brain areas.

Animals↗

Alcohol, nitric oxide, and neurotoxicity: is there a connection?--a review.

A hypothesis is presented to explain the influence of alcohol on glutamate generated excitotoxicity. Chronic alcohol exposure is reported to increase glutamate-N-methyl-D-aspartate (NMDA) receptors and calcium ion channel activity, resulting in the neurotoxicity and seizure activity associated with alcohol withdrawal in certain persons. Recent information indicates that nitric oxide is responsible for the neurotoxicity associated with excessive glutamate stimulation of NMDA receptors. Thus, it is hypothesized that nitric oxide is involved in producing the neurotoxicity and cell disturbances associated with chronic alcohol exposure.

Animals↗

Maternal beer drinking: offspring growth and brain myelination.

The type of alcoholic beverage consumed by pregnant drinkers appears to influence fetal outcome. Beer drinkers are at greater risk than consumers of other alcoholic beverages for having children with fetal alcohol effects (Sixth Special Report to the U.S. Congress on Alcohol and Health, 1987). The magnitude of the risk is increased, because beer is a very popular beverage in our society. Although animal models have been developed to mimic fetal alcohol effect in humans, it is possible that stressful procedures such as intubation, and the hunger of pair-fed animals matched to animals drinking ethanol in liquid diet have interfered with obtaining a pattern of alcohol intake which closely matches that of humans. A majority of the animal models used for alcohol studies have provided ethanol for intake, rather than alcoholic beverages such as beer, which is favored by humans. Thus, a new model for voluntary beer drinking by rats is presented here for use in the study of maternal beer drinking during gestation, and the subsequent developmental consequences in the offspring. Female Long Evans rats (N = 45) were tested by beer preference and assigned to beer drinking (BR) or control groups. All animals were given standard laboratory diet and water ad libitum. BR dams were provided ad libitum access to beer. A pair-fed group (PF) was given non-alcoholic beer with dextrin added to match the caloric intake of the BR animals. Control animals (CT) were given free access to food and water. Control groups included beer preferring animals as well as non-preferring animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Lactational ethanol exposure: brain enzymes and [3H]spiroperidol binding.

Long-Evans lactating rats were fed 27% calories as ethanol in a liquid diet to determine whether alcohol received through the milk would alter normal brain development in the offspring. On days 16, 21 and 30, brains of the female offspring were removed, corpus striatum dissected and assayed for choline acetyltransferase activity, glutamic acid decarboxylase activity and [3H]spiroperidol binding activity. At day 16, there were no differences among the three treatment groups for the enzyme activities assayed. At day 21, glutamic acid decarboxylase activity in the pairfed group was higher than in ET and CT groups. Choline acetyltransferase activity in PF group was higher when compared to ad libitum controls and [3H]spiroperidol binding was not affected. At 30 days of age, animals exposed to ethanol had higher choline acetyltransferase activity and [3H]spiroperidol binding activity when compared to pairfed and ad libitum controls; and higher glutamic acid decarboxylase activity when compared to ad libitum controls. Data from the present study suggest that ethanol exposure during the brain growth spurt has a toxic effect on the late development of dopaminergic, cholinergic and GABAergic systems in the corpus striatum. These results may be related to the clinical symptoms of hyperactivity and problems with motor control in children exposed to alcohol during the third trimester and during lactation.

Animals↗

Brain myelination in the offspring of ethanol-treated rats: in utero versus lactational exposure by crossfostering offspring of control, pairfed and ethanol treated dams.

Pregnant Long-Evans rats were received on day 5 of gestation and divided into 4 treatment groups: (1) 27% calories provided as ethanol in a liquid diet; (2) pairfed i.e., isocaloric liquid diet restricted to match group (1); (3) liquid diet provided ad libitum; and (4) laboratory chow and water provided ad libitum. Litters were culled to 8 pups at birth and crossfostered across dams in all 4 groups to provide offspring falling into 16 different experimental groups, including some exposed to ethanol in utero only and some exposed only during lactation. At birth, blood alcohol levels of dams, culled pups and alcohol levels in the stomach contents of culled pups were measured. All pups were weaned and fed laboratory chow and water ad libitum from 21 days onward. At ages 16, 21, 30 and 52 days, pups were sacrificed, and organ/body weight ratios and brain myelin concentrations were determined. Ethanol treated dams had longer gestational periods. The offspring of ethanol treated dams which were crossfostered to pairfed and well nourished dams during lactation had delayed eye opening, persistent lag in body growth and slightly lower brain myelin concentrations. Offspring of dams which were either pairfed or well nourished during gestation, but crossfostered during lactation to ethanol treated dams, had abnormal organ weights, abnormal brain weights and severely depressed brain myelin concentrations persisting through 52 days of age. Thus, lactational ethanol effects on brain myelin were more severe than gestational effects; body growth was affected more severely by gestational exposure, and gestational effects were generally less severe with adequate nutrition.

Alcoholism↗