bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Prenatal Ethanol and Stress on Levels of β‐Endorphin in Different Brain Regions of the Rat
Authors: Baker Ross A. , Shoemaker William J.
Published: April 2006

The combination of prenatal ethanol exposure and footshock stress was investigated for its effects on brain β‐endorphin levels. Subjects were offspring of rats that received 1 of 3 prenatal dietary treatments: an ethanol‐containing liquid diet, a identical liquid diet with ethanol substituted isocalorically with maltose‐dextrin (pair‐fed group), and standard laboratory rat chow (chow‐fed group). Two different stress paradigms were used: a short (30‐sec) footshock stress paradigm and a prolonged (180‐sec) footshock stress paradigm. Levels of β‐endorphin were measured with radioimmunoassay in eight brain regions of unstressed (baseline) rats, and of stressed rats at 3 and 30 min following termination of the stress. Seven brain regions containing high densities of β‐endorphin axons and terminals were chosen, as well as the arcuate region of the hypothalamus, the only brain region where bothβ‐endorphin perikarya and terminals are located. Following the short footshock stress paradigm, there were no changes in β‐endorphin levels, except for a trend toward increased levels in the pair‐fed group. After the prolonged stress paradigm, levels of β‐endorphin in both the pair‐fed and chow‐fed groups tended to be decreased in several brain regions, including the arcuate region, at 3 min after termination of the stress. In contrast, for the prenatally ethanol‐exposed group, β‐endorphin levels were increased significantly in the arcuate region, and moderately increased in the septal/preoptic region and medulla/pons at 3 min after the prolonged stress paradigm. In the hypothalamus, there was a modest decrease in β‐endorphin levels in all three treatment groups, and little change in β‐endorphin levels at any time after stress in the amygdala, thalamus, and midbrain regions. The decrease in peptide levels in pair‐fed and chow‐fed rats following stress is interpreted as release of the peptide from terminal stores. The failure of the prenatally ethanol‐exposed group to demonstrate this release in the arcuate region, the septal/preoptic region, and the medulla/pons may be related to loss of homeostatic control, seen in behavioral studies of prenatally ethanol‐exposed rats, and in human children with the fetal alcohol syndrome.
Low Doses of Ethanol Impair Spatial Working Memory and Reduce Hippocampal Theta Activity
Authors: Givens Bennet
Published: April 2006

Low doses of ethanol can alter neural activity in the septohippocampal pathway, a pathway critical for spatial working memory. The present study was designed to determine whether acute ethanol induces impairments in working memory and disrupts septohippocampal function as measured by the hippocampal theta rhythm. Rats were preoperatively trained on delayed alternation. A within‐subject design was used to evaluate the effects of ethanol (0.25,0.5, 0.75 and 1.0 g/kg, intraperitoneally) on performance 10 min and 90 min after injection as compared with preinjection baseline. Ethanol produced dose‐, delay‐, and time‐dependent impairments in working memory as indicated by a change in choice accuracy in the delayed alternation task. Ethanol did not affect performance time, the ability to complete the task, or response bias. Thus, the impairment does not appear to result from a decrement in general performance, but rather from an impairment in spatial working memory. Hippocampal theta activity was suppressed by ethanol at the same doses, 0.75 g/kg and 1.0 g/kg, that impaired working memory. The interaction of ethanol with functions of the septohippocampal pathway are discussed.
Low‐Dose Effect of Ethanol on Locomotor Activity Induced by Activation of the Mesolimbic System
Authors: Milton Grace V. , Randall Patrick K. , Erickson Carlton K.
Published: April 2006

Four experiments were designed to study the ability of 0.5 g/kg ethanol (EtOH) intraperitoneally to modify locomotor activity induced by drugs that interact with different sites in the mesolimbic system (MLS) of male Sprague‐Dawley rats. Locomotor activity was measured in a doughnut‐shaped circular arena after various treatments. EtOH alone did not alter locomotor activity in any of the experiments. Amphetamine (AMP, intraperitoneally or intraaccumbens) increased locomotor activity in a dose‐dependent manner, and the presence of EtOH attenuated AMP‐induced locomotor activity. Bilateral infusion of GABAA antagonist picrotoxin (PIC) into the ventral tegmental area also increased locomotor activity in a dose‐dependent manner, and the presence of EtOH attenuated PIC‐induced locomotor activity. On the other hand, the interaction between bilateral infusion of μ‐receptor agonist Tyr‐D‐Ala‐Gly‐NMe‐Phe‐Gly‐ol (DAGO) and EtOH on locomotor activity is complex. The highest dose of DAGO that significantly increased locomotor activity was not affected by the presence of EtOH. But, with lower doses of DAGO that either had no effect or a small increase in locomotor activity, the combination of EtOH and DAGO increased and attenuated locomotor activity, respectively. Results from this study support our hypothesis that a low dose of EtOH that does not modify behavior can interact with neurotransmitter systems in the brain and modify drug‐induced locomotor activity. Modification of this drug‐induced locomotor activity by a low dose of EtOH is dependent on the rate of ongoing locomotor behavior induced by drug and the neurotransmitter substrate that the drug modified to induce locomotor behavior. Based on the results, we speculate that a low dose of EtOH probably interacts with dopaminergic and GABAergic neurotransmitter systems and not with opiopeptidergic systems in the MLS.
Possible Central Adenosinergic Modulation of Ethanol‐Induced Alterations in [14C] Glucose Utilization in Mice
Authors: Anwer Jaseem , Dar M. Saeed
Published: April 2006

The possible role of brain adenosine in acute ethanol‐induced alteration in glucose utilization in the whole brain, as well as in the specific brain areas (cerebellum and brain stem), was investigated. Mice were killed 20‐min postethanol, and the fresh tissue slices (300 μ m) of brain and/or specific brain areas were incubated for 100 min in a 5.5 mm glucose medium in Warburg flasks using [6‐14C]glucose as a tracer. Trapped 14CO2 was counted to estimate glucose utilization. Ethanol (2 g/kg, ip) markedly increased the glucose utilization in whole brain and in both motor areas of brain. Theophylline (50 mg/kg, ip), an adenosine antagonist, significantly reduced ethanol‐induced increase in glucose utilization in whole brain, as well as in brain areas. However, adenosine agonist N6‐cyclohexyladenosine (CHA; 0.1 mg/kg, ip) on the contrary, significantly accentuated ethanol‐induced increase in glucose utilization in these tissues that was nearly completely blocked by theophylline pretreatment. Theophylline alone did not produce any significant change in glucose utilization, whereas CHA alone (in vivo and in vitro) significantly increased glucose utilization, as well as ethanol‐induced increase in glucose utilization in an additive manner. Relevant supportive data were obtained by experiments in which adenosine deaminase (ADA), p‐sulfophenyltheophylline (8‐SPT), and CHA were administered in vitro to the slice preparations. Both ADA and 8‐SPT were effective in almost completely blocking the ethanol‐induced increase in glucose utilization, whereas CHA further enhanced the ethanol‐induced increase in glucose utilization in an additive manner. Collectively, data seemed to suggest an adenosinergic modulation of ethanol‐induced increase in glucose utilization in whole brain, as well as in the cerebellum and brain stem via specific adenosine receptors.
Impaired Delay Eyeblink Conditioning in Amnesic Korsakoff s Patients and Recovered Alcoholics
Authors: McGlinchey‐Berroth Regina , Cermak Laird S. , Carrillo Maria C. , Armfield Susan , Gabrieli John D. E. , Disterhoft John F.
Published: April 2006

The performance of amnesic Korsakoff patients in delay eyeblink classical conditioning was compared with that of recovered chronic alcoholic subjects and healthy normal control subjects. Normal control subjects exhibited acquisition of conditioned responses (CRs) to a previously neutral, conditioned tone stimulus (CS) following repeated pairings with an unconditioned air‐puff stimulus, and demonstrated extinction of CRs when the CS was subsequently presented alone. Both amnesic Korsakoff patients and recovered chronic alcoholic subjects demonstrated an impairment in their ability to acquire CRs. These results indicate that the preservation of delay eyeblink conditioning in amnesia must depend on the underlying neuropathology of the amnesic syndrome. It is known that patients with amnesia caused by medial temporal lobe pathology have preserved conditioning. We have now demonstrated that patients with anmesia caused by Korsakoff's syndrome, as well as recovered chronic alcoholic subjects, have impaired conditioning. This impairment is most likely caused by cerebellar deterioration resulting from years of alcohol abuse.
Thyrotropin and Prolactin Responses to Thyrotropin‐Releasing Hormone in Young Men at High or Low Risk for Alcoholism
Authors: Garbutt James C. , Miller Linda P. , Mundle Linda , Senger Michael , Mason George A.
Published: April 2006

A reduced thyrotropin (TSH) response to TSH‐releasing hormone (TRH) has been reported in a portion of abstinent alcoholic men without evidence of cirrhosis of the liver. It is not known whether this neuroendocrine change is a precursor of alcoholism or a sequelae of heavy alcohol consumption. Three of four published studies have found evidence for differences in TRH‐induced TSH response in subjects at high risk for alcoholism, based on family history, compared with subjects at low risk for alcoholism. To test further the hypothesis that the TRH‐induced TSH response is a vulnerability marker for alcoholism, we tested 25 young men with an alcoholic father [family history‐positive (FHP)] and matched them, on alcohol consumption, to 25 young men with no identified first‐ or second‐degree relatives with alcoholism [family history‐negative (FHN)]. FHP subjects were further categorized based on whether their father had shown signs of alcohol problems before age 25 years (FHP‐Early, n= 10) or after age 24 years (FHP‐Late, n= 12). FHP subjects did not differ from FHN subjects in their baseline levels of thyroid hormones, glucose, Cortisol, or TSH. However, the distribution of TSH responses in the FHP subjects was skewed toward lower values, compared with FHN subjects (p= 0.12). Furthermore, FHP‐Late subjects had lower TSH responses than FHN subjects (p= 0.02), whereas the TSH response of FHP‐Early subjects was not different from FHN subjects. Prolactin responses to TRH were similar across all groups. These findings support the hypothesis that the TRH‐induced TSH response may be a marker of vulnerability to alcoholism and suggest an association between the marker and risk for late‐onset alcoholism.
Retrospective Self‐Report of Alcohol Consumption: Test‐Retest Reliability by Telephone
Authors: Cohen B. Beth , Vinson Daniel C.
Published: April 2006

The Timeline Follow‐Back (TLFB) is an interview technique for obtaining detailed retrospective self‐reports of alcohol consumption with excellent reliability for various composite variables when both administrations are in person. Because the telephone offers practical advantages over face‐to‐face interviewing for follow‐up assessments in longitudinal studies of problem drinkers, this study was undertaken to compare the test‐retest reliability of a 12‐week TLFB interview when the second administration was by telephone to that when the second interview was in person. In addition, because the reliability of the TLFB has been previously assessed using composite variables, we examined the reliability of the TLFB at the item level. Research participants were 30 adult medical patients who drank frequently, and 75 college students who were problem drinkers. Test‐retest reliability as measured by intraclass correlation was generally high, 0.79 or greater for the number of days of drinking > 6 standard drinks, 0.90 or greater for the number of abstinent days, and 0.80 or greater for the greatest number of drinks consumed on any 1 day, in both the most recent 4‐week interval and in the entire 12‐week interval. Test‐retest correlation coefficients for composite variables derived from the interview data were not systematically affected by whether the second interview was in person or by telephone. Furthermore, item‐level correlations were also substantial. Findings support the use of the telephone for follow‐up interviews, potentially reducing costs of longitudinal studies and facilitating multisite studies with centralized data collection, and lend further general support to the reliability of the TLFB.
Assessing Gender Interactions in the Prediction of Mortality in Alcoholic Men and Women: A 20‐Year Follow‐Up Study
Authors: Lewis Collins E. , Smith Elizabeth , Kercher Carman , Spitznagel Edward
Published: April 2006

This study investigates the predictors of mortality in 259 male and female alcoholics who were psychiatrically hospitalized between 1967 and 1968 and followed for > 20 years. The findings showed that, in addition to age, marital status, medical complications, and non‐antisocial personality comorbidity were important independent predictors of time to death. Data pointed to gender interactions, in that marital disruption tended to be a stronger predictor of mortality in men, and delirium tremens tended to be a stronger predictor of mortality in women. Knowing and understanding that certain events and processes may differentially affect the survival of male and female alcoholics will allow for the development of more individualized and gender‐specific therapeutic interventions.
Voice of the Victims
Authors: Erickson Carlton K.
Published: April 2006

Over the past 10 years, I have been privileged to conduct educational forums for audiences containing many recovering alcoholics or otherwise chemically dependent persons. In these forums about the addictive diseases and their treatment and research possibilities, significant interaction with the audience members occurs. During these interactions, certain anecdotal phenomena seem to predominate. The repetitive nature of these reports suggests the need for systematic investigation. As with editorial comments in major medical journals, observed phenomena and unanswered questions from the victims can be valuable in the generation of testable hypotheses. Perhaps the ideas presented herein will be useful in the development of future research on alcohol abuse and alcoholism.
Bidirectional Selective Breeding for Ethanol Effects on Locomotor Activity: Characterization of FAST and SLOW Mice Through Selection Generation 35
Authors: Shen Elaine H. , Harland Richard D. , Crabbe John C. , Phillips Tamara J.
Published: April 2006

Increased recognition of the advantages of genetic animal models has led to heightened interest in their use and development. A replicated bidirectional selective breeding project has produced lines of mice that differ in their locomotor responses to 2.0 g/kg ethanol. FAST‐1 and FAST‐2 mice are highly stimulated by ethanol (EtOH), whereas SLOW‐1 and SLOW‐2 mice are either not affected or respond with locomotor depression. Current heritability estimates indicate that ±6–8% of the response variance in the FAST lines and 2–10% of the response variance in the SLOW lines is of additive genetic origin. Little systematic response to selection has occurred in recent generations, which implies that the limits of selection have been reached. Analysis of saline activity over 35 generations of selection indicates that baseline activities have not changed during the course of selection in three of the lines, whereas baseline activity of FAST‐1 mice has increased slightly. In EtOH dose‐response studies (0.5–3.0 g/kg), FAST mice had biphasic dose‐response curves, whereas the locomotor activity of SLOW mice was either unaffected or depressed by all doses of EtOH. In addition, FAST mice spent more time in motion, traveled farther per movement, traversed greater distances in the center of the test chamber, and ambulated more quickly than SLOW mice when given EtOH. FAST and SLOW mice differed in EtOH clearance rates; however, the differences were slight relative to the large difference in locomotor response. We encourage the use of FAST and SLOW mice to investigate neurophysiological factors underlying sensitivity to the behavioral effects of EtOH, with a view to further testing of the postulated homology between locomotor stimulant effects and addiction potential of drugs of abuse.
Ethanol Suppresses Growth Hormone‐Mediated Cellular Responses in Liver Slices
Authors: Xu Xiaowei , Ingram Rhonda L. , Sonntag William E.
Published: April 2006

Previous studies indicate that both acute and chronic ethanol administration inhibit protein synthesis and decrease the secretion of insulin‐like growth factor‐1 (IGF‐1). Although IGF‐1 synthesis and secretion are regulated by growth hormone secretion from the pituitary gland, we assessed whether ethanol inhibits tissue response to growth hormone. Liver slices from male Sprague‐Dawley rats were prepared, placed into F‐12 media, and incubated at 37°C with [3H]leucine, and either 0.25 or 1 nM rat growth hormone and 0, 37 (physiological levels), or 175 mM (toxic levels) ethanol. Tissues were removed at 0,15,30, and 60 min. Protein synthesis increased linearly during this time period, and administration of growth hormone (1 nM) significantly increased protein synthetic rate by 48% (p < 0.01), whereas addition of 37 or 175 mM ethanol attenuated the effects of growth hormone (p < 0.01). Analysis of IGF‐1 mRNA indicated a 2‐fold increase in response to growth hormone (p < 0.01), whereas ethanol administration decreased the growth hormone‐induced rise of IGF‐1 mRNA. Ethanol (175 mM) inhibited the release of IGF‐1 into the media (p < 0.05). Ethanol did not alter growth hormone receptor binding, and exposure of tissue slices to ethanol did not influence the number of growth hormone receptors or the affinity of growth hormone for its receptor.

Our results demonstrate that (1) growth hormone is a potent acute regulator of IGF‐1 mRNA and IGF‐1 peptide release, (2) ethanol inhibits growth hormone‐induced protein synthesis and induction of IGF‐1 gene expression, and (3) the inhibitory effects of ethanol on growth hormone occur without changing growth hormone receptor number or binding characteristics. We conclude that ethanol suppresses growth hormone‐induced signal transduction, resulting in a decrease in IGF‐1 gene expression.
Synapse‐to‐Neuron Ratio in the Lateral Geniculate Nucleus of Rats Exposed Chronically to Ethanol
Authors: Kjellström C. , Conradi N.
Published: April 2006

Effects of chronic ethanol exposure on synapse‐to‐neuron ratio in the rat lateral geniculate nucleus were investigated. Male Sprague‐Dawley rats were exposed to ethanol, using the Lieber‐DeCarli liquid diets, for 4 months starting at the age of 5 weeks. Brains were per‐fusion‐fixed, and the region containing the dorsal lateral geniculate nucleus was cut into slabs (500 μm thick) that were epoxy resin‐embedded. From each rat, three slabs containing the structure were serially sectioned for electron microscopy. Using the double disector method, the study shows an unaltered synapse‐to‐neuron ratio in ethanol‐treated rats when compared with controls. The findings are in agreement with previous studies on the visual system using the seme exposure model. In contrast, a previous study has shown that the synapse‐to‐neuron ratio in locus ceruleus of ethanol‐treated rats is reduced by 50%. Other studies have shown that, whereas the glutamatergic NMDA receptor is very sensitive to ethanol, the kainate/AMPA type of receptor is very much less so. Thus, the difference in ethanol‐induced synapse elimination between the two regions may reflect this different sensitivity of the glutamatergic receptors, which are of the kainate/AMPA type in the lateral geniculate nucleus and of the NMDA type in the locus ceruleus.
Combined Inhibitory Effects of Ethanol and Adenosine on the Responses of Rabbit Platelets to Thrombin
Authors: Rand Margaret L. , DaCosta Sheila M. , Chahil Amar , Kinlough‐Rathbone Raelene L
Published: April 2006

We have previously shown that acutely administered ethanol, resulting in blood alcohol concentrations of 40‐00 mM, inhibits experimentally induced arterial thrombosis in rabbits. This inhibition by ethanol in vivo is more pronounced than that observed on stimulated platelets in vitro, when a similar concentration of ethanol is added before an aggregating agent. It may be, then, that ethanol has combined effects in vivo with other inhibitors of platelet function. Adenosine has been found to be an important mediator of some of the in vivo effects of ethanol, and we investigated whether ethanol has combined inhibitory effects with adenosine on thrombin‐stimulated platelet responses in vitro. Aggregation and secretion of [14C]serotonin from washed, prelabeled rabbit platelets, pretreated with aspirin, were studied. Maximal aggregation induced by 0.15 units thrombin/ml was slightly inhibited by 87 mM ethanol; secretion of serotonin was reduced from 24% to 12%. However, when thrombin‐induced aggregation was significantly reduced by 1 μM adenosine, ethanol, at 44 and 87 mM, further inhibited aggregation. Secretion of [14C]serotonin was reduced to <3%, with the combination of adenosine and the higher concentration of ethanol. Ethanol did not increase platelet cyclic AMP (cAMP) above basal levels, nor did it affect the increase in cAMP caused by adenosine. The adenosine receptor antagonist, 8‐phenyltheophylline, at 1 μM, blocked the inhibitory effects of adenosine on platelet responses and prevented the adenosine‐induced increase in cAMP. Unexpectedly, however, 8‐phenyltheophylline (1–2 μM) did not completely block the combined inhibitory effects of ethanol and adenosine; this incomplete reversal was not associated with increases in cAMP over basal levels. 8‐Phenyltheophylline may by useful in vivo in determining whether ethanol has combined inhibitory effects with adenosine on experimentally induced arterial thrombosis.
Cyanamide‐Associated Alcoholic Liver Disease: A Sequential Histological Evaluation
Authors: Yokoyama Akira , Sato Shinkichi , Maruyama Katsuya , Nakano Masayuki , Takahashi Hisao , Okuyama Keiji , Takagi Satoshi , Takagi Toshikazu , Yokoyama Tetsuji , Hayashida Motoi , Ishii Hiromasa
Published: April 2006

This is the first study that we are aware of that followed the his‐topathological progression of the liver disease that was caused by the combination of both chronic alcohol use and cyanamide, an an‐tidipsotropic agent. Two sequential liver biopsy specimens were obtained on 29 alcoholics who relapsed with varying histories of cyan‐amide treatment. Cyanamide induced ground‐glass inclusions (GGIs) in the hepatocytes. Two groups were identified, depending on whether GGIs proliferated or regressed, which was, in turn, found contingent on the duration of cyanamide treatment and the drug‐free period. Group 1 included 14 cases in which GGIs either emerged only in the second biopsy specimen or else were increased in the second specimen as compared in the initial specimen. Group 2 composed of 15 cases in which GGIs were either not observed in either specimen or decreased in the second specimen as compared in the initial specimen. Acidophilic bodies were sequentially increased in five cases (36%) of group 1 and in none of group 2. The severity of portal inflammation worsened in 10 cases (71%) of group 1 but in 2 cases (13%) of group 2, although the changes in fibrotic process did not differ between two groups. These differences could not be explained on the basis of the daily ethanol consumption and the length of relapses of the two groups. Thus, when cyanamide‐treated alcoholics relapsed, the combined effect of cyanamide and alcohol produced the development of acidophilic bodies and portal inflammation along with the emergence of GGIs.
Permanent Neuronal Cell Loss in the Inferior Olive of Adult Rats Exposed to Alcohol during the Brain Growth Spurt: A Stereological Investigation
Authors: Napper Ruth M. A. , West James R.
Published: April 2006

The purpose of this study was to examine whether exposure of rat pups to alcohol postnatally over a period of brain development similar to that of the human 3rd trimester results in a permanent loss of cells in the inferior olivary nucleus. It was hypothesized that a deficit of neurons in the inferior olive, the sole source of climbing fibers, may contribute to the cerebellar dysfunction observed following exposure to alcohol during development.

Sprague‐Dawley rat pups were artificially reared and administered alcohol over postnatal days 4–9. One artificially reared group received a daily alcohol dose of 4.5 g/kg, administered as a 10.2% solution in 2 of 12 daily feedings (10.2% group). This pattern of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance. The other artificially reared group was fed a diet made isocaloric to the alcohol‐containing diet (gastrostomy control group). Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of neurons in the inferior olivary nucleus was estimated using unbiased stereological methods.

Exposure to alcohol resulted in a significant deficit in the number of neurons in the inferior olive at 115 days of age. The total number of neurons in the alcohol‐exposed group was 40.12 ± 8.7 ± 103, compared with 53.37 ± 3.7 ± 103 in the artificially reared controls.

These results indicate that there is a permanent deficit of neurons in the inferior olive after postnatal exposure to alcohol. This supports the hypothesis that cerebellar dysfunction after exposure to alcohol during the brain growth spurt may be the result of more extensive neuronal deficits than previously thought.
Effects of Chronic Alcohol Consumption and Aging on Dopamine D1 Receptors in Fischer 344 Rats
Authors: Woods James M. , Ricken John D. , Druse Mary J.
Published: April 2006

The present study examined the hypothesis that chronic alcoholism augments the age‐related loss of dopamine D1 receptors. This hypothesis was investigated because previous studies reported that both aging and chronic alcoholism produce significant changes in dopaminergic systems, and because chronic alcoholism potentiates some age‐related CNS losses. In addition, this study investigated the effects of aging on D1 receptors in animals 1 and 7 days after withdrawal from chronic ethanol. Quantitative autoradiography was used to measure [3H]SCH 23390 binding to D1 receptors in brain areas associated with both the nigrostriatal and mesocorticolimbic dopamine systems. Receptors were assessed in 5‐, 14‐, and 24‐month‐old male Fischer 344 rats that were pair‐fed a control or 6.6% (v/v) ethanol‐containing liquid diet for 6 weeks.

The results of these studies demonstrated that aging is associated with a significant decline in D1 receptors in the rostral and caudal striatum, and substantia nigra of both control and ethanol‐fed rats. These receptor changes in the nigrostriatal system may be associated with motor abnormalities. In addition, there was an age‐related decline in D1 receptors in two brain areas of the mesocorticolimbic system: the nucleus accumbens and frontal cortex. The latter findings may be important because of the involvement of this system with the rewarding properties of ethanol and other drugs of abuse. There were no age‐related differences in the response of D1 receptors to ethanol withdrawal in the caudal and rostral striatum, substantia nigra, and nucleus accumbens. Consumption of the 6.6% (v/v) ethanol‐containing liquid diet for 6 weeks did not augment any of the age‐related losses of D, receptors. Nonetheless, we cannot eliminate the possibility that either a more prolonged ethanol exposure or consumption of a higher dose of ethanol would have had more pronounced effects on the young to aged rats.
Automatic Activation of Alcohol Concepts in Response to Positive Outcomes of Alcohol Use
Authors: Weingardt Kenneth R. , Stacy Alan W. , Leigh Barbara C.
Published: April 2006

Seventy‐one subjects with various levels of drinking experience completed a computerized semantic priming task. Prime phrases (describing positive outcomes of drinking alcohol or neutral phrases) were presented immediately before a target word (either alcohol‐related or not). The results replicated earlier basic research examining the effects of semantically related primes on the processing of subsequent words. Furthermore, the results provided evidence that, for heavy drinking subjects, the presentation of phrases describing positive drinking outcomes significantly primed, or facilitated, responses to the alcohol‐related words. These results are consistent with the view that for some individuals, thoughts about certain outcomes automatically prime, or make accessible, concepts related to alcohol use. An increase in the accessibility of these concepts has important implications for behavioral decisions about alcohol consumption.
Auditory Event‐Related Potentials in Fetal Alcohol Syndrome and Down's Syndrome Children
Authors: Kaneko W. M. , Ehlers C. L. , Philips E. L. , Riley E. P.
Published: April 2006

Abnormal or borderline electroencephalograms are commonly observed in cases of gross mental retardation. However, fewer studies have focused on the use of event‐related responses to aid in the differential diagnosis of developmental cognitive disorders. Fetal alcohol syndrome (FAS) and Down syndrome represent the most common known causes of mental retardation in the Western world. Although Down syndrome is easily diagnosed with a chromosome assay, FAS can be more difficult to diagnose since the diagnostic features are more subjectively based. The present study is the first to characterize auditory event‐related potentials (ERPs) in children with FAS and contrast them to subjects with Down syndrome and controls. A passive auditory “oddball‐plus‐noise” paradigm was utilized to elicit ERPs. Parietal P300 latencies in response to the noise‐burst stimuli for the FAS children were significantly longer, as were the P300s from all cortical sites in Down syndrome subjects in response to the both the infrequent tone and noise‐burst stimuli when compared with the controls. Frontal P300s in Down syndrome children were significantly larger in amplitude compared to the controls and FAS children in response to the infrequent tone. A discriminant function analysis also revealed that these children could be correctly classified as being either Down syndrome, FAS, or normal controls using measures of latency and amplitude of the P300. These data suggest that an evaluation of ERP characteristics may provide a better understanding of the differences between FAS and Down syndrome children, and prove to be an aid in the early identification of children with FAS. These results demonstrate neurophysiological differences between FAS and Down syndrome, and suggest that P300 amplitude and latency data collected from a passive ERP task may be helpful in the discrimination of developmental cognitive disorders.
High Diastolic Blood Pressure: Common Among Women Who Are Heavy Drinkers
Authors: Seppä Kaija , Laippala Pekka , Sillanaukee Pekka
Published: April 2006

The present study evaluates the relationship of different alcohol consumption levels to blood pressure among women. Blood pressure values were compared between four groups of women consuming different amounts of alcohol. Three groups were formed from the middle‐aged female population participating in a health survey (n= 219): 15 consecutive alcohol abstainers, 136 consecutive moderate drinkers, and 68 consecutive heavy drinkers. Also, 78 consecutive female alcoholics reporting for treatment were included, forming the fourth group. The prevalence of systolic blood pressure ≥160 mm Hg did not increase in relation to alcohol consumption. In contrast, the percentage of women showing diastolic blood pressure ≥90 mm Hg clearly increased (p= 0.004) from abstainers (7%) to moderate drinkers (18%), to heavy drinkers (32%), and to alcoholics (37%). The highest blood pressure values were found among heavy drinkers. Compared with abstainers, the mean difference in systolic blood pressure was –12 mm Hg, with a 95% confidence interval from –2 to –23 mm Hg. For diastolic blood pressure, the difference was –6 mm Hg with a 95% confidence interval from 1 to –13 mm Hg. Among alcoholics, the blood pressure values had returned essentially to normal after 4 days of abstinence. It is concluded that alcohol consumption increases both systolic and diastolic blood pressure values among women. However, only diastolic blood pressure values increase enough to be clinically significant. Moderately elevated diastolic blood pressure, combined with normal systolic blood pressure, might thus be a possible sign of alcohol abuse among women. Abstinence should be emphasized as an inexpensive and rapidly effective treatment for mild hypertension among female alcohol abusers.
Characteristics of Japanese Alcoholics with the Atypical Aldehyde Dehydrogenase 2*2.I. A Comparison of the Genotypes of ALDH2, ADH2, ADH3, and Cytochrome P‐4502E1 Between Alcoholics and Nonalcoholics
Authors: Nakamura Kazuhiko , Iwahashi Kazuhiko , Matsuo Yoshinori , Miyatake Ryousuke , Ichikawa Yoshiyuki , Suwaki Hiroshi
Published: April 2006

We examined the genotypes of the aldehyde dehydrogenase (ALDH)‐2, alcohol dehydrogenase (ADH)‐2, ADH3, and P‐4502E1 loci of 53 alcoholics and 97 nonalcoholics. All of the subjects fulfilled the DSM‐III‐R criteria for alcohol dependence. The control group consisted of 97 subjects who were either hospital staff or students. We also compared the frequencies of homozygous ALDH2*1/1 and heterozygous ALDH2*1/2 genotypes in alcoholics. Our study revealed differences in the allelic frequencies of the ALDH2, ADH2, and ADH3 loci between alcoholics and nonalcoholics. For alcoholics with both homozygous ALDH2*1/1 and heterozygous ALDH2*1/2 genotypes, it was found that ADH2 and ADH3 played important roles. Alcoholics with the heterozygous ALDH2*1/2 genotype showed a significantly higher frequency of ADH2*1/1 than ones with the homozygous ALDH2*1/1 genotype. We assume ADH2*1 plays an important role in the development of alcoholism in alcoholics with the heterozygous ALDH2*1/2 genotype.
Chronic Alcoholics without Wernicke‐Korsakoff Syndrome or Cirrhosis Do Not Lose Serotonergic Neurons in the Dorsal Raphe Nucleus
Authors: Baker K. G. , Halliday G. M. , Kril J. J. , Harper C. G.
Published: April 2006

Despite the considerable evidence that alcoholics have perturbation of serotonergic function, there is little pathological evidence for alcohol directly affecting the nervous system. The present study aims to assess neuronal loss that occurs as a consequence of alcohol neurotoxicity in the serotonergic dorsal raphe nucleus (DRN). To that end, the brains of eight alcoholics and eight age‐matched control cases were carefully screened to eliminate serious liver disease, the sequela of thiamine deficiency, Wernicke‐Korsakoff syndrome (WKS), and other pathological abnormalities. Brains were formalin‐fixed for 2 weeks, cut, and then immunohistochemically stained using a monoclonal PH8 antibody specific for the rate‐limiting enzyme of serotonin synthesis, tryptophan hydroxylase. The morphology of the serotonin‐synthesizing neurons and their average size was similar in all cases. However, there was a reduction in the staining intensity of the reaction product in the DRN serotonergic neurons of most alcoholics. Neuronal counts on spaced serial sections revealed that there were an estimated average total of 106,100 ± 19,500 serotonergic neurons in the DRN of alcoholics and 108,300 ± 11,800 in the DRN of controls, indicating that in most alcoholics there is no reduction in the number of these neurons. Therefore, the effect of chronic alcohol consumption on the serotonergic system, in the absence of WKS or liver disease, seems to be functional rather than neuropathological.
Effects of Chronic Ethanol Exposure on Oral Self‐Administration of Ethanol or Saccharin by Wistar Rats
Authors: Schulteis Gery , Hyytiä Petri , Heinrichs Stephen C. , Koob George F.
Published: April 2006

The study of alcohol abuse traditionally has placed great emphasis on the development of tolerance and dependence as key factors. However, animal models of ethanol self‐administration in dependent rats have been difficult to establish, caused in part by ethanol's aversive taste cues and subsequent aversive effects (i.e., “hangover” malaise) that prevent substantial ethanol consumption. In this study, this problem was addressed in animals trained to self‐administer ethanol (10% w/v) in a sweetened‐solution fading procedure before induction of dependence and repeated exposure to withdrawal. Once stable rates of responding for ethanol were achieved, a palatable liquid diet containing 8.7% (v/v) ethanol was introduced as the sole source of calories and fluid for one group of rats [ethanol diet (ED) group]. A second group of rats received a control diet with sucrose isocalorically substituted for ethanol (CD group). After 14–17 days of liquid diet exposure, the rats were withdrawn once a week for 4 weeks and 8 hr into each withdrawal session were allowed to self‐administer ethanol or water for 60 min. As compared with CD rats, ED rats showed significantly greater intake of ethanol, but not water. No significant differences were found when separate groups of ED/CD rats were allowed to self‐administer an alternate reinforcer (0.0075% saccharin solution). Rats who consistently had blood alcohol levels (BALs) above 100 mg% at the time of withdrawal sustained high levels of ethanol self‐administration throughout the four withdrawal sessions. In contrast, rats who had an average BAL at withdrawal below 100 mg% showed progressive decreases in ethanol self‐administration during repeated withdrawal episodes. The results demonstrated that chronic exposure to ethanol and repeated periods of abstinence are accompanied by elevated rates of ethanol intake in certain animals, and the persistence of elevated self‐administration behavior of individual rats is predicted by their BAL at the time of withdrawal.
Failure to Find Exon 7 Polymorphism of the ADH7 Gene in Chinese, Japanese, African‐Americans, and Caucasians
Authors: Carr Lucinda G. , Zeng Daisy , Li Ting‐Kai
Published: April 2006

Class IV alcohol dehydrogenase (σ‐ADH) activity has been found in high levels in the stomach and esophagus, but not in liver. Gastric ADH activity has been reported to influence blood alcohol levels after oral ethanol ingestion, suggesting that σ‐ADH activity plays a role in first‐pass metabolism. It has also been reported that women have lower σ‐ADH activity than men and that Asians have lower σ‐ADH activity than Caucasians and African‐Americans. A genetic basis for these gender and ethnic differences in σ‐ADH activity has been postulated. A recent study in a Japanese subject found a point mutation in the codon for amino acid 287 of the ADH7 gene (which encodes (σ‐ADH), changing the amino acid from glycine to valine. A polymerase chain reaction‐sequencing assay was established to determine the frequency of this polymorphism in the Asian, Caucasian, and African‐American populations. The polymorphism was not present in the 21 Asians, 15 Caucasians, and 3 African‐Americans we genotyped, suggesting that if this polymorphism exists, its frequency is low in these ethnic groups. It is therefore unlikely to be responsible for the absence of σ‐ADH activity in gastric specimens from Asians.
Relationships between Depressive Symptoms, Anxiety, Alcohol Consumption, and Blood Pressure: Results from the CARDIA Study
Authors: Jones‐Webb Rhonda , Jacobs David R. , Flack John M. , Liu Kiang
Published: April 2006

Objectives: We examined cross‐sectional relationships among depressive symptoms, anxiety, alcohol intake, and blood pressure. Test hypotheses were that: (1) alcohol intake, depressive symptoms, and anxiety would be positively related to blood pressure; (2) depressive symptoms and anxiety would have a stronger association with alcohol intake in Blacks than in Whites; and (3) adjustment for differences in depressive symptoms, anxiety, and alcohol intake would reduce Black‐White blood pressure differences. Methods: Study hypotheses were tested in a sample of 4,352 Black and White adults, participating in the CARDIA study. Hypotheses were tested using multiple linear regression. Results: Alcohol intake was positively related to systolic (p= 0.0001) and diastolic (p= 0.0004) blood pressure in men, but not in women. Depressive symptoms and anxiety were unrelated to blood pressure. The relationship between alcohol intake and depressive symptoms differed by race/ethnicity in men (p= 0.0719) and in women (p= 0.0002). Alcohol intake increased with increasing levels of depressive symptoms, but the increase was greater in Blacks than in Whites. After accounting for alcohol intake, body mass index, and other variables, Black‐White blood pressure differences were reduced in men, but not in women; most of the reduction was caused by body mass index. Conclusions: Blacks may respond differently than Whites to psychological distress.
Assessing Alcohol Problems in Female DWI Offenders
Authors: Parks Kathleen A. , Nochajski Thomas H. , Wieczorek William F. , Miller Brenda A.
Published: April 2006

The severity of alcohol problems in a sample of 812 women driving while intoxicated (DWI) offenders enrolled in a Drinking Driver Program in New York State was assessed through the use of multiple measures. These women voluntarily provided information through a self‐administered questionnaire completed at the beginning of the program. Classification of alcohol problems based on DSM‐III‐R criteria was compared with classification based on the use of alcohol‐specific and nonalcohol‐specific measures of alcohol‐related problems. Greater hostility and a larger number of drinks ever consumed accounted for nearly 12% of the variance between no diagnosis and alcohol abuse women, whereas these two variables plus age, race, depression, and having a relative with alcohol problems accounted for nearly 41% of the variance between alcohol abuse and dependent women. A subsample of women within each DSM‐III‐R diagnostic group showed high risk for later, more severe alcohol problems. Multiple measures of alcohol problems help to elucidate subtle differences in alcohol problems within each of the broad categories specified by the DSM, and should facilitate more appropriate intervention and treatment plans for women DWI offenders with alcohol‐related problems.
Effects of Gender and Comorbidity on Problem Drinking in a Community Sample
Authors: Lewis Collins E. , Bucholz Kathleen K. , Spitznagel Edward , Shayka Joseph J.
Published: April 2006

We investigated the influence of gender, comorbidity, drinking history, and age on the clinical manifestations of DSM‐III alcohol abuse and/or dependence in men and women. The sample was drawn from the National Institute of Mental Health Epidemiologic Catchment Area study, a large‐scale, multicenter survey to investigate psychiatric disorders in the community. The results showed that gender and comorbidity had independent effects on problem drinking after drinking history and age had been taken into account. Gender contributed to the age of onset of problem drinking and the rate of its development. Comorbidity, drinking history, and age contributed independently to its severity. The effects of these variables in this community sample paralleled those reported in treatment samples.
Pharmacological Treatment for Antisocial Personality Disorder Alcoholics: A Preliminary Study
Authors: Penick Elizabeth C. , Powell Barbara J. , Campbell Jan , Liskow Barry I. , Nickel Elizabeth J. , Dale Tamara M. , Thomas H. Mikel , Laster Louise J. , Noble Elizabeth
Published: April 2006

A short time ago, we reported that a subgroup of hospitalized alcoholic men with comorbid antisocial personality disorder (ASP) seemed to benefit significantly from antidepressant medication at the end of a 6‐month period in a double‐blind, random assignment, placebo‐controlled study. In a reanalysis of those data, we divided the ASP alcoholic group (n= 29) into those who did (n= 15) and who did not (n= 14) also satisfy DSM‐III‐R criteria for an additional current mood and/or anxiety disorder and then compared the 6‐month outcomes of these two smaller subgroups. Despite the small ns, the results for most drinking outcome measures indicated: (1) that ASP alcoholics with a current mood/anxiety disorder improved significantly more with pharmacological treatment, relative to placebo; and (2) that ASP alcoholics with no current mood/anxiety disorder failed to respond differentially to pharmacological treatment over the 6‐month period. These findings suggest a possibly useful and inexpensive approach to the long‐term management of a very difficult‐to‐treat subgroup of men substance abusers.
Postbinge Effects of Acute Alcohol Intoxication on Hepatic Free Radical Formation
Authors: Bautista Abraham P. , Spitzer John J.
Published: April 2006

The present studies were performed to test the hypothesis that Kupffer and endothelial cells are activated after recovery from an acute alcohol binge, which is accompanied by formation of oxygen‐derived radicals. These radicals have been implicated in the pathogenesis of alcohol‐mediated tissue injury in a number of organs. Male Sprague‐Dawley rats received an intravenous injection of 20% ethanol in saline (1.75 g/kg), followed by an intravenous infusion (250 to 300 mg/kg/hr) for 12 hr. At the end of 12‐hr infusion, ethanol was replaced by saline, and the infusion was continued for a further 6 hr. This was referred to as the recovery period. The 6‐hr recovery period was selected because superoxide anion generation by the perfused liver peaked at this time point. Superoxide anion formation by the perfused liver was measured by the superoxide dismutase‐inhibit‐able reduction of ferricytochrome c. Kupffer and endothelial cells were isolated for the determination of in vivo glucose uptake and in vitro superoxide anion release. Results show that a significant (p < 0.05) amount of superoxide (1.54 nmol/min/g) was generated by the perfused liver at 6 hr recovery after 12 hr of ethanol infusion. Serum ALT activity was also elevated in this treatment group. Time‐matched control‐saline infused animals or ethanol‐treated animals without a recovery period released <0.2 nmol/min/g of superoxide. The postrecovery superoxide production and an accompanying increase in the in vivo glucose uptake were also observed in isolated Kupffer and endothelial cells. Depletion of Kupffer cells by gadolinium chloride before ethanol treatment and recovery was associated with significant attenuation of free radical formation by the perfused liver and reduction of serum ALT. These studies demonstrate that recovery from an acute alcohol binge has a stimulating effect on hepatic sinusoidal superoxide production, and it may also affect liver function.