bluuebunny/crossref_metadata_2025 huggingface dataset:
Paternal and Maternal Alcohol Consumption: Effects on Offspring in Two Strains of Rats
Authors: Abel Ernest L.
Published: April 2006

Long‐Evans and Sprague‐Dawley male rats were given liquid alcohol diets containing 35%, 17.5%, or 0% ethanol‐derived calories (EDC). The latter two groups were pair fed to the higher alcohol diet group. A fourth group received lab chow and water ad libitum to assess the role of paternal undernutrition associated with alcohol consumption. After three or four weeks of diet Consumption, these males were bred to females of the same strain. Pregnant females were divided into similarly treated alcohol groups and were fed these diets beginning on gestation Day 8, thus creating a factorial study with strain, paternal, and maternal alcohol consumption as main factors.

Paternal alcohol consumption was associated with decreased litter size, decreased testosterone levels, and a strain‐related effect on offspring activity. Offspring activity decreased for those sired by 35% and 17.5% EDC Long‐Evans fathers. Activity also decreased for offspring sired by 17.5% EDC Sprague‐Dawley fathers but increased for those sired by 35% EDC fathers. Paternal alcohol consumption did not affect postnatal mortality or passive avoidance learning of offspring.

Maternal alcohol consumption was associated with lower birth weights, lower offspring weights at weaning, increased postnatal mortality, and poorer passive avoidance learning. However, offspring activity was not affected.

In a separate study, levels of alcohol in the testes were found to be somewhat, but not significantly, lower than blood alcohol levels. DNA taken from sperm of Long‐Evans males consuming alcohol, migrated farther under pulsed field electrophoresis than DNA from control fathers, suggestive of an alcohol‐related effect on sperm DNA.
Swift Increase in Alcohol Metabolism in Humans
Authors: Thurman Ronald G. , Cheren Isa , Forman Donald , Ewing John A. , Glassman Edward
Published: April 2006

One hundred and fifteen human male subjects, 19–30 years of age, received ethanol orally as vodka (0.55, 0.7, or 0.85 g/kg) followed by a second drink (0.3–0.4 g/kg) given 3–4 hr later. After both doses, blood ethanol levels reached approximately 100 mg/dl. Breath samples were taken every 20‐30 min and rates of ethanol elimination were determined. In addition to the design described above, 100 subjects received 0.7 g/kg ethanol in two separate visits to the laboratory. In a third experimental design, ethanol was given i.v. to 12 subjects. With the single‐day experimental design, the frequency distribution of changes in rates of ethanol elimination between the first compared with the second administration of ethanol was not unimodal. Up to 20% of the subjects demonstrated rates more than 40% greater than basal values in response to ethanol. Based on these findings in humans, a Swift Increase in Alcohol Metabolism (SIAM) was defined as an increase in the rate of ethanol elimination of at least 40% over the basal rate. Under these conditions, the frequency of SIAM was dose dependent (studied with 0.55, 0.7, and 0.85 g/kg); nearly 20% of the subjects demonstrated SIAM with a dose of ethanol of 0.85 g/kg. In the two‐day experimental design, a SIAM response was also observed in about 10% of 49 well‐fed subjects; however, none of 51 subjects tested exhibited a SIAM response following an overnight fast. In addition, a rapid and transient SIAM reflecting a 60% increase in the rate of ethanol elimination above basal values was observed when ethanol was given continuously for 5 hr i.v. Thus, differing rates of absorption of ethanol cannot explain the activation of ethanol metabolism in humans by ethanol. Interestingly, subjects classified as SIAM in these studies reported fewer drinking problems in first and second degree relatives than subjects who did not demonstrate a SIAM response. Further, 3.2% of the non‐SIAM subjects had a positive family history for alcoholism while none was reported in the SIAM group. These data demonstrate that SIAM exists in humans and suggest that it may be a trait that may protect some individuals against problem drinking and alcoholism.
Nucleotide Sequence of the ADH23 Gene Encoding the Human Alcohol Dehydrogenase β3 Subunit
Authors: Carr Lucinda G. , Xu Yiling , Ho Wei‐Hsien , Edenberg Howard J.
Published: April 2006

All nine exons of the ADH23 allele, which encodes the human alcohol dehydrogenase β3 subunit, have been cloned and sequenced. Comparison of this sequence to the ADH21 nucleotide sequence revealed only a single difference that results in an amino acid change, thus proving that the significant kinetic differences between these two isozymes is due to the Cys for Arg substitution at position 369. There are also two silent polymorphisms, and two changes in noncoding regions.
Comparative Study on Ethanol Elimination and Blood Acetaldehyde between Alcoholics and Control Subjects
Authors: Adachi Junko , Mizoi Yasuhiko , Fukunaga Tatsushige , Ogawa Yumi , Imamichi Hiroyuki
Published: April 2006

Factors influencing ethanol elimination rate and Mood acetaldehyde concentration with regard to age, blood ethanol concentration, and degrees of alcoholic liver disorder were studied in alcoholic patients vis‐à‐vis healthy subjects.

Ninety‐four male alcoholic patients were divided into five groups according to age and into three groups according to blood ethanol concentration which ranged between 4.21 and 0.29 mg/ml. It was noted that as age increased, Mood ethanol concentration decreased. Groups A, B, and C consisted of subjects whose ethanol levels were more than 2.5, between 1.0 and 2.5, and less than 1.0 mg/ml, respectively. Average values of ethanol elimination rate in Groups A, B, and C were 0.26, 0.23, and 0.18 mg/ml/hr, respectively. The rate Increased as blood ethanol concentration elevated. The rate In group B was significantly higher than that in the healthy control subjects who had blood ethanol levels between 1.0 and 2.5 mg/ml. The rate of ethanol elimination was independent of liver disorder judged by liver function test values.

Blood acetaldehyde concentrations in the patients were less than 1.48 μg/ml, with an average value of 0.58 μg/ml, and were significantly correlated with blood ethanol levels in both alcoholics and healthy subjects.
Prenatal Ethanol Exposure Alters Steroidogenic Enzyme Activity in Newborn Rat Testes
Authors: Kelce W. R. , Rudeen P. K. , Ganjam V. K.
Published: April 2006

We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague‐Dewley rats were fed a liquid ethanol diet (35% ethanol‐derived eateries), a pair‐fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5‐ene‐3β‐hydroxysteroid dehydrogenase/isomerase or C17,25‐lyase, the enzymatic activity of 17α‐hydroxytase was significantly (p < 0.01) reduced (i.e., approximately 36%) in the ethanol‐exposed pups compared to those from (tie pair‐fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17α‐hydroxylase activity from the ethanol‐exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 80). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.
Effect of Ethanol on the Social Behavior of Group‐Housed and Isolated Mice
Authors: Hilakivi L. A. , Lister R. G.
Published: April 2006

The interaction between isolation and the response to ethanol was investigated with a social behavior test and a loss of righting reflex paradigm. The time a pair of mice spent in active social interaction, aggressive behavior, and avoidance‐irritability showed an isolation‐related increase, while locomotor activity was not affected by 0‐10 days of isolation. Ethanol (0.8 g/kg) reduced the social interaction time in mice isolated for 10 days and 2.0 g/kg ethanol reduced it in all groups. Ethanol induced a locomotor stimulatory effect both in group‐housed and isolated animals. An aggression‐inducing effect of 0.8 g/kg ethanol was observed only in mice isolated for 5 days, while mice isolated for 10 days reduced their aggressive behavior after this dose of ethanol. The loss of righting reflex after 3.5 g/kg ethanol did not appear to vary with isolation. The results suggest that isolation alters some effects of ethanol qualitatively (e.g., its effects on aggressive behavior) but leaves other effects (e.g., its locomotor stimulant and hypnotic effects) unchanged.
Derivation and Validation of a Prediction Rule for Identifying Heavy Consumers of Alcohol
Authors: Lichtenstein Michael J. , Burger M. Candice , Yarned John W. G. , Elwood Peter C. , Sweetnam Peter M.
Published: April 2006

Using two population‐based cohorts of men aged 45‐59, we sought to derive and validate a prediction rule for identifying heavy consumers of alcohol. Eighty‐five percent of eligible men on electoral rolls in Caerphilly, Wales (derivation set, N = 2512) and 90% of eligible men on the practice lists of 16 Speedwell, England, general practitioners participated (validation set, N = 2348).

Alcohol consumption was assessed by questionnaire with heavy alcohol consumption defined as the top 10% of the Caerphilly population's alcohol usage (>525 cc ethanol per week).

The prediction rule, Score = (mean corpuscular volume × 1.00) + (body mass index × 0.31) + (systolic blood pressure × 0.08) + HDL‐cholesterol × 9.24) + (fasting triglyceride × 2.20) was derived by multiple linear regression in the Caerphilly cohort and validated in the Speedwell cohort. Comparing the lower 20% of the Score distribution with the upper 5%, likelihood ratios increased from 0.15 to 5.29 and 0.06 to 7.42 in the Caerphilly and Speedwell cohorts, respectively. Having a score of 136.30 or greater yielded a relative risk of being a heavy drinker of 23.1 (95% CI = 10.1‐53.0) in Caerphilly and 99.3 (95% CI = 12.8‐769.5) in Speedwell. The derived prediction rule is a valid diagnostic aid to help clinicians identify heavy alcohol consumers.
Conditioned Opponent Responses: Effects of Placebo Challenge in Alcoholic Subjects
Authors: McCaul Mary E. , Turkkan Jaylan S. , Stitzer Maxine L.
Published: April 2006

The present study continues a series of studies examining a number of variables that contribute to the demonstration of conditioned responses to alcohol in alcoholics. We pursued here the hypothesis that subjects receiving placebo in an environment previously associated with alcohol ingestion would exhibit conditioned responses as compared with subjects who had only received placebo in the environment. Further, we predicted that these conditioned responses would be opposite in direction to responses obtained during active drink sessions. Twelve subjects received active alcohol during session Days 1 through 4 and a placebo challenge on Day 5; the second group received placebo throughout sessions 1 through 5. On Day 1, heart rate and skin conductance were elevated following active alcohol ingestion as compared with placebo. On Day 5 following the placebo challenge, these physiological responses were significantly lower in the alcohol group as compared with the placebo group; the reversal of effects on Day 5 is suggestive of conditioned compensatory responses. Also, following the placebo on Day 5, desire to drink scores of the alcohol group were greater than those of the placebo group. The present data suggest that subjects exhibit conditioned compensatory responses when the environment signals alcohol availability. Results are consistent with Siegel's model of conditioned compensatory responses to repeated drug administration, and may help to account for some aspects of tolerance development and conditioned withdrawal.
Alcohol Effects on Cognitive and Personality Style in Women with Special Reference to Primary and Secondary Process
Authors: Gustafson Roland , Källmén Håkan
Published: April 2006

Changes in primary and secondary process functioning as well as in experienced locus of control as indicators of cognitive style were examined as a function of alcohol intoxication. Women subjects drank 1.0 ml of pure alcohol/kg body weight and were compared to a placebo and a control group. Results indicated a significant shift in locus of control toward greater externality and a significant shift in cognitive style from a dominance of secondary process when sober to a dominance of primary process when intoxicated. These shifts were discussed as indicative of the pharmacological properties of alcohol and were related to the disinhibition and the arousal hypotheses. Alternative explanations were also discussed.
Mechanistic and Functional Divergence Between Thyrotropin‐releasing Hormone and RO 15‐4513 Interactions with Ethanol
Authors: McCown Thomas J. , Breese George R.
Published: April 2006

Both thyrotropin‐releasing hormone (TRH) and RO 15‐4513 antagonize ethanol‐induced depression, but this common property does not Infer that both compounds share similar mechanisms of action. In the present studies, both TRH (30 mg/kg, I.p.) and RO 15‐4513 (10 mg/kg, I.p.) reversed ethanol‐induced depression of locomotor activity, in accord with previous reports. However, the benzodiazepine antagonist, RO 15‐1788, blocked this action of RO 15‐4513, while exerting no effect on the analeptic action of TRH. Using a model of seizure activity electrically elicited from the inferior colliculus, ethanol exerted a dose‐related attenuation of seizure activity. This anticonvulsant action of ethanol was not altered by TRH (30 mg/kg, I.p.), but RO 15‐4513 (3 mg/kg) reversed the effect of the 0.5, but not the 1.0 g/kg, dose of ethanol. In addition, pretreatment with RO 15‐4513 (1 or 3 mg/kg, I.p.), but not TRH (30 mg/kg, I.p.), caused seizure generalization into the forebrain following inferior collicular stimulation, further verifying the proconvulsant properties of RO 15‐4513. In conclusion, the analeptic action of TRH appears independent of benzodiazepine activity, and in contrast to RO 15‐4513, TRH does not exhibit proconvulsant properties. Furthermore, because TRH did not antagonize both depressant actions of ethanol studied, it appears unlikely that TRH directly interacts with the molecular basis of ethanol action.
Exposure of Rats to Ethanol from Postnatal Days 4 to 8: Alterations of Cholinergic Neurochemistry in the Hippocampus and Cerebellum at Day 20
Authors: Light Kim E. , Serbus Dellan C. , Santiago Melissa
Published: April 2006

Brief neonatal ethanol exposure (3.0 g/kg/dose, twice daily; postnatal day (PN) 4 to PN8) resulted in cholinergic neurochemical alterations in the cerebellum, but not the hippocampus of rats assayed on PN20. Analysis revealed that the binding affinity of cerebellar muscarinic receptors for [3H]quinuclidinyl benzilate was decreased by ethanol, but only in female pups. Other gender‐specific but treatment‐independent cerebellar differences were identified as well, including lower levels of choline acetyltransferase activity and St‐level (1,000 × g) crude protein in males and females, respectively.

No evidence of ethanol‐induced cholinergic change was noted in the hippocampus of the same pups on PN20. However, collapsed across treatment, male hippocampi were found to contain less S1‐level protein than their female counterparts.

Neither muscarinic receptor density nor acetyl cholinesterase activity were found to differ between treatments or genders, in either brain region. Consistent with the developmental timetables for regional cholinergic synaptogenesis in the rat, observations on PN20 confirm a hypothesis of cerebellar cholinergic vulnerability and hippocampal cholinergic resilience to neonatal ethanol insult.
Long‐Term Recovery in Alcoholics
Authors: De Soto Clinton B. , O'Donnell William E. , De Soto Janet L.
Published: April 2006

A cross‐sectional study of alcoholics who varied widely in duration of abstinence was combined with a four‐year follow‐up study of the same subjects. Together, the data demonstrated a course of recovery in abstinent alcoholics measured in three ways: severity of symptoms, probability of relapse, and work history. Additionally, the subjects showed high rates of smoking cessation. By every measure, the course of recovery seemed essentially the same in men and women. The recovery process was most rapid in the early years of abstinence but continued for 10 or more years. It was suggested that keys to full recovery in alcoholics are abstinence and time, which are necessary for recovery from a protracted withdrawal syndrome and brain dysfunction, for the repair of social relationships, for vocational rehabilitation, and for abstinence itself to become stable.
Effects of Social Drinking and Familial Alcoholism Risk on Cognitive Functioning: Null Findings
Authors: Alterman Arthur I. , Hall Julia G.
Published: April 2006

The effects of both heavy social drinking and high familial alcoholism risk status on the cognitive performance of college men were examined in this study. A two by three factorial design was employed represented by two social drinking groups (heavylnonheavy) and three familial risk groups (high, middle, and low). The cognitive performance tasks employed–group embedded figures, revised Beta mazes, mirror tracing, and symbol‐digit paired associate learning–had all been previously shown to present difficulties to male alcoholics. No evidence was obtained of a relationship between heavy drinking or familial risk and cognitive functioning, nor a meaningful interaction of these two independent variables. Little evidence was revealed for the “hangover hypothesis” as evidenced by a relationship between drinking behavior within the past week and cognitive performance. The findings are discussed in the context of previous findings in these areas and the general difficulties of interpretation posed in nonexperimental research based on subject variables.
Effects of Ethanol on Human Platelets Stimulated with Platelet‐Activating Factor, a Biologically Active Ether Phospholipid
Authors: Baker Rodney C. , Fish H. T. , Fitzpatrick Frank A.
Published: April 2006

The interaction between ethanol and 1–0‐alkyl‐2‐acetyl‐sn‐glycerol‐3‐phosphocholine (platelet activating factor, PAF) was addressed using platelets obtained from normal nonalcoholic volunteers. Ethanol at concentrations of 20 to 100 mM inhibited PAF activation of human platelets. Ethanol inhibited prominently the second or arachidonic acid metabolite dependent wave of platelet aggregation, which occurs with human platelets in citrated plasma. It also inhibited serotonin release and thromboxane AP formation associated with this secondary phase of aggregation. Ethanol did not readily inhibit the primary wave of PAF‐induced aggregation. The incorporation of PAF into platelets or metabolism of PAF was not influenced by up to 100 mM ethanol. Since ethanol inhibited only the secondary response, a direct interaction between PAF, ethanol, and a platelet PAF receptor is unlikely. The effect of ethanol on PAF‐induced platelet aggregation shows a selectivity similar to that demonstrated by other investigators for epinephrine and adenosine diphosphate.
Metric Analysis of Hippocampal Granule Cell Dendritic Trees After Alcohol Withdrawal in Rats
Authors: Cadete‐Leite A. , Tavares M. A. , Aives M. C. , Uylings H. B. M. , Paula‐Barbosa M. M.
Published: April 2006

It was previously demonstrated that after prolonged alcohol consumption, dendrites might display either degenerative or plastic changes according to the central nervous system areas studied. Furthermore, and rather unexpectedly, we also found that withdrawal from alcohol led to a decrease of the relative number of granule cells in the fascia dentata. Thus, it seemed worthwhile to quantify, using a semiautomatic measuring system, the dendritic arborizations of hippocampal granule cells of rats alcohol‐fed for 12 months followed by 6 months of abstinence and compare the results with age‐matched control and alcohol‐fed groups. The results indicate smaller dendritic trees in the abstinent group when compared with the higher values of the dendritic parameters found in alcohol‐fed rats.
Xanthine Oxidase Status in Ethanol‐Intoxicated Rat Liver
Authors: Abbondanza Ada , Battelli Maria Giulia , Soffritti Morando , Cessi Carlo
Published: April 2006

The status of xanthine oxidase in ethanol‐induced liver injury has been investigated in the rat, by acute and chronic ethanol treatments. A 38% increase of the enzyme O‐form was observed after repeated ethanol administration. Chronic intoxication caused a significant decrease of total xanthine oxidase activity after both prolonged ethanol feeding and life span ethanol ingestion. The intermediate D/O‐form of xanthine oxidase (that can act either as an oxidase or as a dehydrogenase, being able to react with O2 as well as with NAD+ as electron acceptor14,16) increased 5.5‐fold after prolonged ethanol feeding.
Studies of Whole Blood Associated Acetaldehyde as a Marker for Alcohol Intake in Mice
Authors: Peterson C. M. , Scott B. K.
Published: April 2006

Thirty C57Bl mice were randomized into two groups. Group 1 sewed as controls while Group 2 was given 10% V/V ethanol with the drinking water. Whole blood‐ associated acetaldehyde (WBAA) was measured on capillary blood samples using a fluorigenic high performance chromatographic assay. WBAA peaked at Day 2. A stable mean plateau of 263 ± 71 SD with a range of 160–400 nmoles/g hemoglobin WBAA was found in the group consuming ethanol compared with 122 ± 17 SD and a range of 88–150 nmoles/g hemoglobin for controls (p < 0.001). When ethanol was discontinued, levels of WBAA declined and became similar to those of controls by 9 days following cessation of ethanol. The quantitative difference between ethanol‐consuming and control animals and also the rapid rise of whole blood‐associated acetaldehyde and the relatively slow decline following cessation of ethanol intake indicate that such a test might be a useful monitor of drinking behavior.
Alcohol as a Nutrient: Interactions Between Ethanol and Carbohydrate
Authors: Guthrie George D. , Myers K. Jeffrey , Gesser Edward J. , White Gary W. , Koehl Jack R.
Published: April 2006

This study examined metabolic interactions between two nutrients—ethanol and carbohydrate. Both nutrients are metabolized by a common pathway to fatty acids from acetyl‐coenzyme A by lipogenic enzymes. The effects of ethanol and carbohydrate on the induction of lipogenic enzymes in livers of rats were examined using two types of base diets differing in carbohydrate and lipid content and using isocaloric substitutions of ethanol, carbohydrate, and fat. Three nonlipogenic enzymes were used for comparison. lsocaloric substitution of both fat and carbohydrate for ethanol was necessary to show the specific effects of alcohol on the activity of lipogenic or nonlipogenic enzymes. Carbohydrate, and not ethanol, induced lipogenic enzymes. Ethanol specifically reduced the activity of lactate dehydrogenase and malic enzyme, but did not affect those of alcohol dehydrogenase or glycerol 3‐phosphate dehydrogenase. Ethanol interacted with carbohydrate to increase the activity of ATP citrate lyase. In addition, we studied the effects of ethanol and different kinds of carbohydrates on the growth of rats and on the morphology of their livers and intestines. Ethanol significantly decreased growth characteristics (weight gain, growth rate, and caloric efficiency). Fructose, either as a monosaccharide or in sucrose, decreased this alcohol effect. Sucrose was better than glucose in lowering lipid accumulation in livers of rats. Fragility of intestinal villi was found with an alcohol, low carbohydrate diet, but was not present in alcohol diets with a higher level of carbohydrate. In contrast to carbohydrate, ethanol lacked some characteristics of a nutrient, namely, it did not induce some enzymes involved in its metabolism and did not promote optimum growth.
Potentiation of Cocaine‐Mediated Hepatotoxicity by Acute and Chronic Ethanol
Authors: Boyer C. Scott , Petersen Dennis R.
Published: April 2006

Cocaine has been associated with hepatotoxicities in man and is potent hepatotoxin in mice. The theorized toxic metabolite of cocaine is thought to be generated by a multistep pathway mediated primarily by cytochrome P‐450. Ethanol, whether administered acutely or chronically, is known to have diverse effects on numerous hepatocellular biochemical pathways. The present study was designed to characterize not only the effects of acute and chronic ethanol on cocaine‐mediated hepatotoxicity but also on the hepatic reduced glutathione (GSH) in an attempt to correlate depletions of GSH with changes in toxicity. Male and female mice were administered an acute 50 mg/kg dose of cocaine either 1 hr after an acute 3 g/kg dose of ethanol, or after 5 days of consuming an ethanol‐containing liquid diet. Serum alanine aminotransferase (ALT) activity was measured in blood collected 24 hr after the acute cocaine dose. In addition, hepatic reduced glutathione (GSH) and cytochrome P‐450 content were measured at the point in the pretreatment where cocaine was administered. The results of this study indicate that both acute and chronic ethanol pretreatment can markedly enhance the hepatotoxicity of cocaine in both male and female mice and that the enhancement is significantly greater after chronic ethanol pretreatment. Hepatic GSH was slightly decreased 1 hr after an acute dose of ethanol and significantly decreased after chronic ethanol consumption. The correlation of this biochemical parameter with enhancement of toxicity is complicated, however, by the observation that hepatic GSH levels in isocaloric controls to the chronic ethanol animals exhibited an approximate 50% decrease while their postcocaine ALT levels were unchanged in females and markedly attenuated in males. Significant induction of cytochrome P‐450 occurred only in the mice chronically consuming ethanol. These results suggest that the mechanism of the potentiation of cocaine‐mediated hepatotoxicity by acute ethanol is not directly related to alterations in the cellular GSH stores and that potentiation by chronic ethanol consumption does not depend solely on GSH depletion.
Use of Leukocyte Aldehyde Dehydrogenase Activity to Monitor Inhibitory Effect of Disulfiram Treatment
Authors: Helander Anders , Carlsson Sten
Published: April 2006

Aldehyde dehydrogenase (ALDH; EC 1.2, 1.3) activity was determined in leukocytes and erythrocytes from alcoholic patients during different stages of disulfiram (Antabuse) treatment. Assays were performed by incubating intact isolated blood cells in phosphate‐buffered saline (pH 7.4, 37°C), using 3,4‐dihydroxyphenylacetaldehyde (DOPAL), the biogenic aldehyde derived from dopamine, as substrate. The ALDH activity was assessed from the amount of 3,4‐dihydroxyphenylacetic acid (DOPAC) formed, as analysed by highperformance liquid chromatography with electrochemical detection. The leukocyte ALDH, which is similar to the liver “mitochondrial’low‐Km ALDH isozyme, was maximally inhibited (about 40‐60%) within 2 to 3 days after the initial disulfiram administration (dosage 200 or 400 mg/day orally). The time to reach maximum inhibition (about 95%) of the erythrocyte ALDH, which closely resembles the liver “cytosolic'’high‐Km isozyme, varied from 3 to more than 6 days. When medication was completed, the leukocyte ALDH activity remained unaltered for the first 2 days, and did not revert to normal levels until about 6 to 7 days after terminating treatment. The erythrocyte ALDH was still inhibited by about 90% 1 week after the last disulfiram administration. These results suggest that the leukocyte ALDH activity might provide an easily accessible marker for monitoring effect and time course of ALDH inhibition during disulfiram treatment.
Antagonism of Ethanol Intoxication in Rats by Inhibitors of Phenylethanolamine N‐Methyltransferase
Authors: Mefford Ivan N. , Lister Richard G. , Ota Miyuki , Linnoila Markku
Published: April 2006

The probable involvement of brain epinephrine in the expression of the acute sedative and intoxicating effects of ethanol and pentobarbital is demonstrated. Two selective inhibitors of phenylethanolamine N‐methyltransferase (PNMT), LY 134046 and LY78335, proved to be potent and long‐lasting antagonists of ethanol intoxication in rats. Acute antagonism of pentobarbital‐induced intoxication was observed with LY 134046. The present results are compatible with role for central epinephrine synthesis in ethanol and pentobarbital‐induced sedation and intoxication in rats.
Human Leukocyte β‐Adrenergic Stimulated Cyclic AMP in Ethanol Intoxication and Withdrawal
Authors: Swift R. M. , DePetrillo P.
Published: April 2006

The effects of ethanol were examined on cyclic AMP production in intact human leukocytes in vitro. In leukocytes isolated from alcohol abstinent subjects, ethanol enhances isoproterenol‐stimulated and prostaglandin E1‐stimulated cyclic AMP formation. Without agonist, ethanol is able to stimulate cyclic AMP production at concentrations of 160 mM and above.

Leukocytes isolated from subjects undergoing alcohol detoxification showed increases in basal levels of leukocyte cyclic AMP, in isoproterenol‐stimulated cyclic AMP, and in ethanol‐stimulated cyclic AMP on the 2nd or 3rd day of withdrawal in comparison to the first day of withdrawal and in comparison to abstinent subjects. The data suggest that increased β‐adrenergic activity seen in alcohol withdrawal may be in part due to an increased responsiveness of β‐adrenergic stimulated cyclic AMP in tissues.
Estimation of Genetic Correlation: Interpretation of Experiments Using Selectively Bred and Inbred Animals
Authors: Crabbe John C. , Phillips Tamara J. , Kosobud Ann , Belknap John K.
Published: April 2006

There is increasing interest in determining the extent to which multiple characters related to drug sensitivity are influenced by common genes. The principal method for testing for the existence of such genetic correlations has been examination of pairs of mouse or rat lines selectively bred for sensitivity or resistance to a single behavioral effect of a drug. When a pair of selected lines is found to differ significantly on some trait other than the one on which they were selected, it is commonly concluded that significant genetic correlation between the traits exists, implying the action of a common set of genes on the two responses. In addition, results from comparisons of lines of animals selected for trait X and tested for trait Y may be compared with results from lines selected for trait Y and tested for trait X. As the number of correlated responses in selected lines increases, it becomes more important to adhere to sensible, consensual guidelines for interpreting such line differences. The principles underlying phenotypic and genotypic correlational analyses with selected lines are discussed. A scheme is presented to allow standardization across laboratories of inferences about the relative strength of genetic association from experiments with selected lines. Statistical and practical experimental issues are addressed. Estimates of genetic correlations may also be derived from the correlation of mean trait values across a panel of inbred strains. Existing data have sometimes found estimates of genetic correlations made with one approach to be inconsistent with those estimated in other ways. Possible reasons for this are discussed. Finally, the relationship between phenotypic correlations and genetic corrlations is discussed. Phenotypic and genetic correlations for a pair of traits may differ widely, and may even be opposite in sign. Both are characteristic of the population from which they are sampled. Phenotypic correlations estimated within selected lines may change over time, as the additive genetic variance in the selected trait is exhausted. A specific example of this phenomenon is given.
Serum β‐Hexosaminidase as a Marker of Heavy Drinking
Authors: Kärkkäinen Päivi , Poikolainen Kari , Salaspuro Mikko
Published: April 2006

β‐hexosaminidase, also called n‐acetyl‐β‐d‐glucosaminidase, is a lysosomal glycosidase, which has been found to be increased in the sera of alcoholics admitted to acute detoxification treatment. To study serum β‐hexosaminidase (β‐HEX) as a marker of heavy drinking, it was compared with GGT, ASAT, and ALAT in three study groups: twentyfive drunken arrestees, 16 social drinkers, and 27 teetotallers. Mean serum β‐HEX levels were two times higher among drunken arrestees than among social drinkers or teetotallers. Average daily alcohol intake during the preceding 30 days in the pooled group of drunken arrestees and social drinkers correlated positively (r= 0.69; p < 0.0001) with serum β‐HEX. The sensitivity of β‐HEX in the detection of heavy drinking, defined as over 60 g ethanol daily, was 85.7% compared to 47.6% for GGT. The specificity of β‐HEX was 97.6%. The positive correlations between β‐HEX and ASAT (r= 0.74; p < 0.0001) and ALAT (r= 0.41; p < 0.05) indicate that increased serum β‐HEX level may reflect early liver injury. Serum β‐HEX seems to be a sensitive biological marker of heavy drinking reflecting better the ingested amounts of alcohol than GGT.
The Influence of Sociodemographic Characteristics on Familial Alcohol Problems: Data from a Community Sample
Authors: Russell Marcia , Cooper M. Lynne , Frone Michael R.
Published: April 2006

The moderating influence of race (black versus white), age, sex, and socioeconomic status on the relationship between alcohol abuse/dependence in offspring and a family history of alcoholism/problem drinking was investigated in a representative general population sample (N= 1659). Significant family history by race by age and family history by race by sex interactions were observed when predicting lifetime risk of alcohol abuse/dependence in offspring. Socioeconomic status did not moderate the effect of familial alcoholism/problem drinking on offspring alcohol abuse/dependence. Relative odds ratios indicated that the risk of alcohol abuse/dependence associated with a positive family history increased with increasing age among whites; whereas, it decreased with increasing age among blacks. Among whites, the relative odds ratio for the effect of family history was higher for females than for males; however, among blacks it was higher for males than females. Although these findings need to be replicated in other populations, they suggest that it is important to take race, age, and sex into consideration when investigating familial alcohol problems.
Clinical Characteristics of Female Alcoholics with Low Platelet Monoamine Oxidase Activity
Authors: Hallman Jarmila , von Knorring Anne‐Liis , von Knorring Lars , Oreland Lars
Published: April 2006

The aim of the present study was to see if female alcoholics had low platelet MAO activity and whether there was a correlation between low MAO activity in female alcoholics and specific clinical characteristics often observed in type II male alcoholics. In earlier studies, male alcoholics have been subdivided into type I and type II alcoholics. Type II alcoholics were characterized by early onset, a high frequency of depression and alcoholism in first degree relatives, a high frequency of drug abuse and social complications, sensation seeking behavior, extraversion, impulsive sensation seeking psychopathy, and low platelet MAO activity.

In the present series it was demonstrated that the female alcoholics had significantly lower platelet MAO activities than the female healthy volunteers. The subgroup of female alcoholics with low platelet MAO activity, however, did not differ from female alcoholics with normal platelet MAO activity in the same way as male alcoholics with low platelet MAO activity have been shown to differ from male alcoholics with normal platelet activity. They did not have early onset, higher frequency of depression or alcoholism in their first degree relatives, nor more social complications than the female alcoholics with normal platelet MAO activity. Furthermore, they did not differ from the female alcoholics with normal platelet MAO activity in any personality trait covered by the Karolinska Scales of Personality (KSP).
Hypothalamic‐Pituitary and Thyroid Function in Chronic Alcoholics with Neurological Complications
Authors: Knudsen G. Moos , Christensen H. , Berild D. , Melgaard B. , Kirkegaard C. , Hasselbalch H.
Published: April 2006

Endocrinological tests were performed in 14 chronic alcoholic men with signs of intellectual impairment and/or peripheral neuropathy. All had been abstinent from alcohol for at least 1 month.

Basal serum growth hormone (GH) was consistently increased in only one patient whereas the GH responses to insulin hypoglycemia stimulation was normal in all patients. Thyroid function values (T4, T3, rT3, TSH) were normal in all patients whereas baseline serum prolactin values were significantly increased in alcoholics as compared with a control group. In a combined TRH‐ and GnRH‐stimulation tests, GH‐responses were also normal whereas TSH and prolactin responses were blunted or absent in about half of the patients, the responses correlating significantly (p < 0.01). It is concluded that disturbances in the hypothalamic‐pituitary axis may occur in chronic alcoholics with nervous impairment independently of the physical deterioration, which often is associated with chronic alcoholism.
Differential Reinforcement and Diurnal Rhythms of Lever Pressing for Ethanol in AA and Wistar Rats
Authors: Hyytiä P. , Sinclair J. D.
Published: April 2006

High‐drinking AA (Alko, Alcohol) and moderate‐drinking Wistar rats, after ethanol drinking experience in their home cages, were housed continually in operant chambers with free access to water and food. Ethanol and water could be obtained by lever pressing on a concurrent FR1:FR1 schedule. The AA rats readily learned the operant response for oral ethanol, responded significantly more for ethanol than water, and increased ethanol, responding when the fixed‐ratio schedule for it was increased from FR1 to FR2 and FR4. This indicates that ethanol was serving as a reinforcer for the AAs. In contrast, the Wistars showed little evidence for ethanol reinforcement. Both AAs and Wistars had a three‐peak pattern of ethanol responding during the dark phase, but peaks for the Wistars preceded those for the AAs by 1 or 2 hr. The patterns were similar when on an FR4 schedule, which greatly reduced the amount of alcohol, suggesting that they are not controlled by blood alcohol levels. The difference between the AA and Wistar patterns may, however, be related to the differential ethanol reinforcement.
Temperament Deviation and Risk for Alcoholism
Authors: Tarter Ralph E. , Kabene Mostefa , Escallier Ellen A. , Laird Susan B. , Jacob Theodore
Published: April 2006

Sons of alcoholics and nonalcoholics drawn from a community sample were compared across multiple dimensions of temperament. Sons of alcoholics scored higher on only behavioral activity level. This trait score was found to be unrelated to family environment. The implications of these findings for clarifying alcoholism vulnerability are discussed.
Individual Differences in the Sedating Effects of Ethanol
Authors: Zwyghuizen‐Doorenbos Ardith , Roehrs Timothy , Timms Victoria , Roth Thomas
Published: April 2006

Twenty‐four healthy, normal‐sleeping, males aged 21–35 were screened for basal levels of sleepiness using the Multiple Sleep Latency Test (MSLT). Twelve subjects had basal average daily sleep latencies of ≤6 min (sleepy) and 12 had latencies of ≥16 min (alert) on the MSLT. Subjects consumed either ethanol (0.75 mg/kg) or placebo at 0900–0930 after spending 8 hr time in bed (TIB) the previous night. Sleep latency was measured at 1000, 1200, 1400, and 1600 hr. Divided attention performance and the Stanford Sleepiness Scale (SSS) were assessed at 1100 hr. Breath ethanol concentration (BEC) was determined prior to each latency test. Ethanol decreased average daily sleep latency, divided attention scores and SSS ratings. There were individual differences in the sedating and impairing effects of ethanol, related to subjects' basal level of sleepiness/alertness. The alert subjects exhibited longer sleep latencies and higher performance scores after ethanol administration than the sleepy subjects after placebo. Subjectively the groups had a similar level of sleepiness on placebo and were similarly sedated with ethanol.
Effects of Prenatal Ethanol and Long‐Chain n‐3 Fatty Acid Supplementation on Development in Mice. 2. Fatty Acid Composition of Brain Membrane Phospholipids
Authors: Wainwright P. E. , Huang Y‐S. , Simmons V. , Mills D. E. , Ward R. P. , Ward G. R. , Winfield D. , McCutcheon D.
Published: April 2006

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. The diet also contained 20% oil; this was either of two mixtures, one comprised of predominantly n‐6 (18:2n‐6) fatty acids, and the other containing an equivalent amount of n‐6, but supplemented with a source of long chain n‐3 (20:5n‐3, 22:6n‐3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Birth occurred on day 19, and the fatty acid composition of the brain membrane phospholipids was determined in the pups 3 days after birth (day 22 postconception) and again, 10 days later (day 32 postconception). On day 22 the polyunsaturated fatty acid (PUFA) composition of the brain phospholipids reflected dietary availability, with the n‐3/n‐6 ratio higher in the n‐3 groups; this was decreased by ethanol in the phosphatidylcholine (PC) fraction. The dietary effect was still apparent on day 32; again ethanol reduced this in both the PC and phosphatidylethanolamine (PE) fractions. The n‐3 oil, but not ethanol, increased the 20:3n‐6/20:4n‐6 ratio, indicative of an inhibition of the activity of delta‐5 desaturase. With respect to the 22:C compounds, the n‐3 oil decreased the levels of 22:5n‐6, while increasing those of 22:6n‐3, but generally the sum of these two fatty acids remained unchanged. Ethanol decreased levels of 22:5n‐6, and, on day 32, also decreased those of 22:6n‐3, resulting in a decrease in the sum of these 22:C PUFA.
Corticotropin‐Releasing Factor Is Altered in Brains of Animals with High Preference for Ethanol
Authors: George Susan R. , Fan Teresa , Roldan Luis , Naranjo Claudio A.
Published: April 2006

Ethanol administered to rats has been shown to stimulate the hypothalamic‐pituitary‐adrenal axis. The present study describes alterations in brain CRF neuronal systems that accompanied the voluntary high consumption of ethanol by Wistar rats presented with a free choice between 6% ethanol and tap water. Hypothalamic CRF concentrations (outside median eminence) were significantly increased in animals with a high preference for ethanol whereas concentrations of CRF in neurointermediate pituitary and medullapons were significantly decreased. No changes of CRF levels were evident in median eminence, frontal cortex, midbrain, thalamus, or cerebellum. Brain CRF concentrations in two strains of mice with genetically determined differential alcohol preference were measured. In ethanol‐naive mice, there were documented differences in CRF concentrations, with an increase in frontal cortex levels, and a decrease in medulla‐pons levels in the ethanol‐preferring strain (C57BL/6J) compared to the nonpreferring strain (C3H/CRGL/2). Thus, certain brain CRF neuronal systems are preferentially affected by high ethanol consumption, and pre‐existing differences in these systems may even contribute to the development of a high preference for ethanol.
Initiating Ethanol Drinking in a Simian Social Group in a Naturalistic Setting
Authors: Crowley Thomas J. , Williams Elizabeth A. , Jones Richard H.
Published: April 2006

We examined in nine group‐living, male Japanese Snow monkeys the initiation of alcohol‐drinking behavior in an enriched environment where both social and nonsocial stimuli could influence drinking. The monkeys usually could move freely between an indoor shelter and a large outdoor corral, which contained three drinkometers. During daily 2‐hr sessions in pre‐ and post‐training periods (with food and water available ad libitum), the drinkometers held (on different days) Koolaid‐saccharin, water, water with 5% ethanol, Koolaid‐saccharin with 5% ethanol, or Koolaid‐sucrose with acetic acid (matched in calories and palatability to Koolaid‐saccharin with 5% ethanol). Between pre‐and post‐training periods was a long training period, in which Koolaid‐saccharin with various ethanol concentrations was presented with the daily food ration in 2‐hr drinking sessions. On other selected training days, water with 5% ethanol was presented.

During training sessions some monkeys drank high doses; others did not. During the period of peak drinking, the daily mean ethanol consumption ranged among animals from 0.54‐1.99 ml/kg. Blood ethanol concentrations then sometimes exceeded 100 mg/dl. During the post‐training period, with return to ad libitum food and water, consumption declined from these peaks, but remained significantly higher than pretraining consumption; the ethanol solution was established as a reinforcer. Monkeys differed significantly in the extent of this pre/post increase. In both pre‐ and post‐training periods, consumption was significantly greater when all three drinkometers operated, compared with only one. On pretraining days when only one drinkometer operated, more dominant animals drank significantly more than less dominant animals; this difference disappeared by the post‐training period, as less dominant animals learned to use the drinkometers at times when the dominant animals eschewed the machines. Pretraining consumption did not predict (among animals) post‐training consumption. Before, during, and after training, these animals drank less of both alcohol and control solutions than did members of another species, which we had studied in smaller indoor pens. We discuss possible explanations and implications.
Increased Number of GABAergic Terminals in the Nucleus Accumbens Is Associated with Alcohol Preference in Rats
Authors: Hwang Bang H. , Lumeng Lawrence , Wu Jang‐Yen , Li Ting‐Kai
Published: April 2006

Ethanol is known to be anxiolytic and this effect may be mediated through GABA transmission acting on the GABAA‐benzodiazepine‐CI− ionophore complex. Recent studies from our laboratory have suggested that GABA transmission and the GABAA‐benzodiazepine‐ CI− ionophore complex might be involved in the rewarding action of ethanol in alcohol‐preferring rats. We report here immunocytochemical and morphometric studies analyzing the GABAergic terminal density in the nucleus accumbens (NA), corpus striatum, nucleus tractus solitarius, and lateral septum of the selectively bred P (alcohol‐preferring) and the NP (alcohol‐nonpreferring) lines of rats, as well as of the high‐alcohol‐drinking (HAD) and low‐alcohol‐drinking (LAD) lines of rats. The NA was included for analysis because this structure has been implicated as an important component of the brain reward system. An increase of GABAergic terminal density was found in the NA of the P rats, when compared with the NP rats. Similarly, there were more GABAergic terminals in the NA of HAD rats than of the LAD rats. No differences between the lines were seen in the other brain regions examined. The results suggest that alcohol preference in P and HAD rats may be related to increased GABA terminals and enhanced GABAergic inhibition within the NA.