Alcohol and food self-administration by female Macaque monkeys as a function of menstrual cycle phase

Female Macaque monkeys were trained to self-administer food (1 g banana pellet) and alcohol (0.12 g/kg/inj IV) in an operant paradigm. Alcohol and food-maintained responding were controlled by a second order schedule of reinforcement FR 4 (VR 16:S) that required an average of 64 responses for delivery of one food pellet or alcohol injection. Alcohol self-administration at average dose levels of 0-1.5, 1.5-3.0, 3.0-4.0 and 4.0 to 5.5 g/kg/day did not vary systematically as a function of menstrual cycle phase in a sample of 30 menstrual cycles. But alcohol self-administration was significantly lower during menstruation (p less than 0.002) in comparison to mid-cycle or the late luteal phase. Monkeys that self-administered high doses of alcohol (3.0-5.5 g/kg/day) also showed stable patterns of food self-administration across the menstrual cycle. Monkeys that self-administered low to moderate doses of alcohol (0-3.0 g/kg/day) showed a consistent decrease in food self-administration at mid-cycle. The implications of these data for hypotheses concerning estrogen modulation of food intake and the influence of the premenstruum on alcohol self-administration are discussed.     

The relationship between sleep and physical activity: the moderating role of daily alcohol consumption

Study ObjectivesStudies have demonstrated a daily, bidirectional relationship between sleep and physical activity. However, little is known about how other health behaviors, such as alcohol consumption affect this relationship. This study examined how daily and average alcohol consumption affects the relationships between sleep and physical activity.MethodsParticipants included 70 men and women, ages 18–50 with sleep duration >6.5 hours. Participants wore an actigraph, physical activity monitor and recorded number of alcoholic drinks by daily food logs for 7 days. Results were analyzed using multi-level models to evaluate the 7-day average (i.e. between-person effects) and daily effects (i.e. within-person effects) simultaneously.ResultsThose with more average (7 day) minutes of vigorous physical activity had less wake after sleep onset (WASO). Furthermore, a higher number of alcoholic drinks was associated with longer sleep duration and higher WASO over 7 days. Days with a higher number of alcoholic drinks were associated with higher WASO and sleep fragmentation that night. Alcohol intake moderated the average (7 days) and daily relationships between sleep and physical activity such that high average (7 days) WASO was associated with shorter average total physical activity duration, but only for those with higher alcohol intake. In addition, longer physical activity duration during the day was associated with lower sleep fragmentation that night, but only for those with lower alcohol intake.ConclusionsThese data demonstrate that in a naturalistic setting, alcohol intake negatively impacts sleep and diminishes the benefits of physical activity on sleep.     

Adolescent alcohol use is a risk factor for adult alcohol and drug dependence: evidence from a twin design

BACKGROUND: Early alcohol use is associated with abuse and dependence of licit and illicit substances later in life. The role of genetic and environmental factors in this association is not conclusive. METHOD: In 1992, data on substance use, abuse/dependence and psychiatric disorders were collected from 8169 male twin members of the Vietnam Era Twin Registry. The interview obtained age of onset of regular drinking (one drink/month for 6 or more months). Regression analyses of twin pairs discordant for early alcohol use tested whether the association between early drinking (before age 17) and adult substance use and abuse/dependence remained after controlling for genetic factors, family environment and covariates. Twin models tested for common genetic and/or environmental influences on early drinking and adult alcohol dependence and ever use and abuse/dependence on marijuana and other drugs. RESULTS: Co-twin analyses suggested the association between early regular alcohol use and adult alcohol dependence, marijuana and other drug use, and marijuana and other drug abuse/dependence could not be entirely explained by common genetic and shared family environmental factors. Genetic contributions to early regular drinking were significantly correlated with those on use of marijuana (rA=0.59), use of other drugs (rA=0.64), alcohol dependence (rA=0.54) and abuse/dependence of marijuana and other drugs (rA=0.63 and 0.66). Small but significant unique environmental correlations (rE range 0.11-0.22) indicated that familial factors could not entirely explain the association between early alcohol use and later substance use, abuse and dependence. CONCLUSIONS: Early regular drinking is associated with later alcohol dependence and use, abuse/dependence on drugs. The association is not entirely explained by genetic or shared family environmental factors. This suggests unique environmental factors contribute to transitions from early regular alcohol drinking to use, abuse and dependence on alcohol and other substances.     

A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women

In 1980, 87,526 female nurses 34 to 59 years of age completed a dietary questionnaire that assessed their consumption of beer, wine, and liquor. By 1984, during 334,382 person-years of follow-up, we had documented 200 incident cases of severe coronary heart disease (164 nonfatal myocardial infarctions and 36 deaths due to coronary disease), 66 ischemic strokes, and 28 subarachnoid hemorrhages. Follow-up was 98 percent complete. As compared with nondrinkers, women who consumed 5 to 14 g of alcohol per day (three to nine drinks per week) had a relative risk of coronary disease of 0.6 (95 percent confidence interval, 0.4 to 0.9); for 15 to 24 g per day the relative risk was 0.6 (0.3 to 1.1), and for 25 g or more per day it was 0.4 (0.2 to 0.8), after adjustment for risk factors for coronary disease. Alcohol intake was also associated with a decreased risk of ischemic stroke. For 5 to 14 g of alcohol per day the relative risk was 0.3 (0.1 to 0.7), and for 15 g per day or more it was 0.5 (0.2 to 1.1). In contrast, although the number of cases of subarachnoid hemorrhage was small, alcohol intake tended to be associated with an increased risk of this disorder; for 5 to 14 g per day the relative risk was 3.7 (1.0 to 13.8). These prospective data suggest that among middle-aged women, moderate alcohol consumption decreases the risks of coronary heart disease and ischemic stroke but may increase the risk of subarachnoid hemorrhage.     

Blood cells and alcohol consumption with special reference to smoking habits

In the course of the Paris study on risk factors of cardiovascular disease in a large professional group, 7710 active and apparently healthy men aged between 48 and 54 were examined. This study measured the relationship between clinical abnormalities suggesting alcoholic liver disease (ALD) and the following blood parameters: white (WBC) and red (RBC) blood cell counts, haematocrit (H), and mean corpuscular volume (MCV), the former computed as H/RBC ratio. A subsequent analysis was performed on a random sample of 485 subjects without ALD who were questioned on their daily average alcohol consumption. Each subject was classified as ;smoker' or ;non-smoker' according to his daily tobacco consumption for the last five years. Analysis of the data confirmed that smoking and alcohol were related to the blood parameters; but, according to smoking habit, different relationships between alcohol consumption (or ALD) and MCV, RBC, or WBC counts were found: for smokers, RBC count significantly decreased and MCV increased with alcohol consumption (or ALD); for non-smokers, WBC count significantly increased with alcohol consumption (or ALD). So, it would be of interest to consider the relation between alcohol and tobacco in interpreting possible changes in blood parameters and in formulating hypotheses on the mechanisms of their specific action.     

Alcoholic intemperance, coronary heart disease and mortality in middle-aged Swedish men

High alcohol consumption is one of the major risk indicators for premature death in middle-aged men. An indicator of alcohol abuse--registration with the social authorities for alcoholic problems--was used to evaluate the role of alcohol in relation to general and cause-specific mortality in a general population sample. Altogether 1,116 men (11%) out of a total population of 10,004 men were registered for alcoholic problems. Total mortality during 11.8 years' follow-up was 10.4% among the non-registered men, compared to 20.5% among men with occasional convictions for drunkenness and 29.6% among heavy abusers. Fatal cancer as a whole was not independently associated with alcohol abuse, but oropharyngeal and oesophageal cancers together were seven times more common in the alcohol-registered groups. Total coronary heart disease (CHD) was significantly and independently associated with alcohol abuse, but nearly all the excess CHD mortality among the alcohol-registered men could be attributed to sudden coronary death. Cases with definite recent myocardial infarction were not more common in the alcoholic population. A combined effect of coronary arteriosclerosis and heart muscle damage secondary to alcohol abuse is suggested. Other causes of death strongly associated with registration for alcohol abuse include pulmonary embolism, pneumonia and peptic ulcer, as well as death from liver cirrhosis and alcoholism. Of the excess mortality among alcohol-registered subjects, 20.1% could be attributed to CHD, 18.1% to violent death, 13.6% to alcoholism without another diagnosis and 11.1% to liver cirrhosis.     

An hypothesis on the association between maternal smoking and dizygotic twinning

There is good evidence that smoking is a marker for high steroid hormone concentrations (at least at the time that smoking is initiated). This would explain the finding that smoking is associated with dizygotic, though not monozygotic, twinning. The notion that smoking and other elective behaviours (e.g. drinking alcohol, opting for vasectomy and use of oral contraception) are markers or indices of high hormone concentrations may have widespread repercussions for cross- sectional epidemiological studies of such risk factors for diseases thought to be partially caused by high (e.g. prostatic and breast cancers) or low (e.g. rheumatoid arthritis) concentrations of these hormones.      

Effects of social status and moderate alcohol consumption on mammary gland and endometrium of surgically postmenopausal monkeys

OBJECTIVE: To evaluate the effects of social subordination stress and chronic moderate alcohol consumption on indices of breast and endometrial cancer risk. DESIGN: Forty-six adult, ovariectomized, cynomolgus monkeys (Macaca fascicularis) were trained to voluntarily drink a placebo or a two-drink/day equivalent of ethanol (0.5 g/kg), 5 days a week for 26 months, the latter resulting in average blood alcohol levels of 42 mg/100 mL. Indices of cell proliferation and sex steroid receptor abundance were measured. RESULTS: Compared with dominants, socially subordinate females had increased cell proliferation and proportions of glandular (P < 0.02) and epithelial tissue (P = 0.009) and less stroma (P < 0.02) in endometrium, and increased tissue thickness in breast (P < 0.05). There was no evidence of increased risk of breast or endometrial cancer with chronic moderate alcohol consumption, as indicated by markers of cell proliferation and sex steroid receptor abundance. Chronic moderate alcohol consumption did not effect circulating sex steroid concentrations (all P > 0.10). The adipocyte hormones leptin and adiponectin were correlated with indices of cell proliferation and sex steroid receptor abundance. CONCLUSIONS: These observations suggest that social status was more important than chronic moderate alcohol consumption in endometrial and breast biology of surgically postmenopausal females. Endogenous sex steroid metabolism was not significantly affected by chronic moderate alcohol exposure consistent with the lack of estrogen-like effects on breast and endometrium. Social subordination stress was associated with initial cellular changes that may increase endometrial cancer risk. Ovariectomized cynomolgus monkeys may be a useful model for the study of effects of social factors and obesity on breast and endometrial cancer risk.     

Alcohol abuse prevention in African-American communities.

Because of the devastating morbidity, mortality, and social dislocations associated with alcohol abuse in many African-American communities, the prevention of alcohol abuse represents a critical component of the public health agenda for African Americans. This article reviews African-American cultural issues pertinent to alcohol use and abuse and the information available regarding the excess medical and social complications experienced by African Americans secondary to alcohol abuse. Some recommendations are made for a specific research agenda for the prevention of alcohol abuse with relevance to African Americans.     

Fatty acid ethyl esters in adipose tissue. A laboratory marker for alcohol-related death

Fatty acid ethyl esters, a family of ethanol metabolites, are formed by esterification of ethanol with fatty acids and have been detected in human organs commonly damaged by ethanol abuse. Because alcohol-related deaths may occur up to six times as often as reported on death certificates, we undertook quantitation of these potentially longer-lived alcohol metabolites in postmortem human adipose tissue to assess their usefulness as a measure of recent ethanol exposure. After isolation and identification using sequential thin-layer and gas chromatography, fatty acid ethyl esters were present in adipose tissue of chronic alcoholics (mean +/- SEM equals 300 +/- 46 nmol/g), even though blood ethanol concentration at the time of death was undetectable. Unintoxicated nonalcoholic subjects who had no history of alcohol abuse had concentrations seven times lower (mean +/- SEM equals 43 +/- 13 nmol/g). In vitro studies demonstrate that fatty acid ethyl esters are synthesized by human adipose tissue in proportion to the ethanol concentration present and their half-life in adipose tissue of laboratory animals is 16 +/- 1.6 hours, ie, fourfold greater than that of alcohol. These results indicate that fatty acid ethyl esters are long-lived ethanol metabolites whose persistence and accumulation in adipose tissue may allow an accurate diagnosis of significant alcohol consumption even when ethanol has been completely eliminated from the body.     

Sudden death in epilepsy: standards of reporting and the value of toxicological analysis

The authors audited the value of toxicology/histology and reporting standards in sudden death autopsy cases in individuals with epilepsy/seizures. Of 83 cases with epilepsy/seizures and no macroscopically obvious cause of death, 40 had no history of drug/alcohol abuse. Toxicological analysis was performed in 11/40 (28%) and did not contribute to the cause of death in any. Conversely, in individuals with epilepsy with known drug/alcohol abuse and cases with a history of seizures related to drug/alcohol abuse, toxicological analysis was performed in 17/22 (77%) and 14/21 (67%), contributing to the causes of death in 8/17 (47%) and 10/14 (71%), respectively. Details of seizures were poorly reported, possibly due to a lack of information from the coroner's office, while autopsy findings were recorded diligently. The authors provide an evidence base for the RCPath guidelines and suggest that taking toxicology samples is essential only when there is a history of drug/alcohol abuse or suspicion of overdose.     

Moderate alcohol consumption and the risk of breast cancer

In 1980, 89,538 U.S. women 34 to 59 years of age, with no history of cancer, completed an independently validated dietary questionnaire that included the use of beer, wine, and liquor. During the ensuring four years, 601 cases of breast cancer were diagnosed among cohort members. Among the women consuming 5 to 14 g of alcohol daily (about three to nine drinks per week), the age-adjusted relative risk of breast cancer was 1.3 (95 percent confidence limits, 1.1 and 1.7). Consumption of 15 g of alcohol or more per day was associated with a relative risk of 1.6 (95 percent confidence limits, 1.3 and 2.0; Mantel extension chi for linear trend = +4.2; P less than 0.0001). Adjustment for known breast cancer risk factors and a variety of nutritional variables did not materially alter this relation. Significant associations were observed for beer and liquor when considered separately. Among women without risk factors for breast cancer who were under 55 years of age, the relative risk associated with consumption of 15 g of alcohol or more per day was 2.5 (95 percent confidence limits, 1.5 and 4.2). These prospective data derived from measurements of alcohol intake recorded before the diagnosis of breast cancer confirm the findings of several previous case-control studies. Viewed collectively, they suggest that alcohol intake may contribute to the risk of breast cancer.     

Ethanol intake increases galanin mRNA in the hypothalamus and withdrawal decreases it

Alcoholism can be viewed as a motivational disorder that results from alterations in brain systems for ingestive behavior. Therefore, it was hypothesized that alcohol intake might alter the expression of hypothalamic peptides that stimulate feeding. Earlier studies showed that hypothalamic injection of the feeding-stimulatory peptide, galanin (GAL), increases the release of dopamine (DA) in the nucleus accumbens (NAc), as does systemic alcohol, leading to a focus on GAL. Results of this study demonstrate the following: (1). Ethanol, injected daily (0.8 g/kg 10% v/v) for 7 days in male rats, markedly increased the expression of GAL but not of neuropeptide Y (NPY). This occurred in specific hypothalamic nuclei, namely the dorsomedial nucleus (DMN), paraventricular nucleus (PVN) and perifornical lateral hypothalamus (PLH). (2). Rats induced to drink ethanol ad libitum, by gradually increasing the concentration from 1% to 9% v/v without adding sugar or flavoring, exhibited a similar stimulation of GAL mRNA in the PVN and GAL immunoreactivity in the DMN and PVN. (3). Rats given increasing ethanol concentrations, with 12 h access starting 4 h into the dark cycle, had a mean blood alcohol concentration of 18 mg/dl and exhibited a similar increase in GAL expression in the DMN and PVN. (4) Withdrawal from the opioid effects of 9% ethanol, produced by injection of naloxone (3 mg/kg sc), reversed this ethanol effect by significantly reducing GAL expression in the DMN and PLH below baseline levels. These studies suggest a possible role for hypothalamic GAL in alcohol abuse.     

Of human bondage: food craving,obsession, compulsion,and addiction

Is it more than a linguistic accident that the same term, craving, is used to describe intense desires for both foods and for a variety of drugs of abuse? There is strong evidence for common pathways that are affected by most addictive drugs. As the other contributors to this volume will indicate, a strong case can also be made for some shared substrates for food and drug rewards in animals. There has been less explicit work on this topic in humans but many lines of evidence support the common mechanism view: Opioid peptides seem to influence food palatability for humans. There is mounting evidence for comorbidity between drug/alcohol abuse and excessive craving or liking for sweets. Anecdotally, elderly individuals tend to 'age-out' of drug abuse, and the elderly also experience markedly fewer food cravings with age. If we focus on the compulsive aspects of food and drug cravings, there is also evidence for overlap: for example, activity in the orbitofrontal cortex is associated with cocaine and alcohol craving. This area is also implicated in the pathology of obsessive-compulsive disorder. Although there is no direct evidence of orbitofrontal involvement in food cravings, there is indirect evidence such as higher than expected co-occurrence of obsessive-compulsive behavior and eating disorders. As a result of bringing together evidence for common substrates for food and for drug rewards, we hope to be able to advance fundamental knowledge of motivational processes and to promote the development of better treatments for drug addiction and for eating disorders.     

Dynamic daily associations between insomnia symptoms and alcohol use in adults with chronic pain

Individuals with chronic pain are at risk for sleep disruption and heavy alcohol use, yet the daily associations between these behaviours are not well characterized. This study aimed to determine the extent to which alcohol use affects insomnia symptoms and vice versa in adults reporting symptoms of chronic pain. Participants were 73 individuals (93% women) reporting alcohol use in addition to symptoms of insomnia and chronic pain. They completed daily diaries assessing insomnia symptoms and alcohol use for 14 days. Multilevel modelling was used to evaluate the bidirectional associations between alcohol use and insomnia symptoms at the daily level. Consistent with laboratory‐based research, alcohol use was associated with decreased sleep‐onset latency the same night but increased sleep‐onset latency 2 nights later. Specifically, for every alcoholic drink consumed, time to sleep onset decreased by 5.0 min in the same night but increased by 4.3 min 2 nights later. Alcohol use was not significantly associated with subsequent wake after sleep onset or total sleep time, and insomnia symptoms were not significantly associated with subsequent alcohol use. To our knowledge, these data provide the first evidence that alcohol use negatively affects insomnia symptoms up to 2 days post‐consumption in patients reporting symptoms of insomnia and chronic pain. Findings suggest that one drink will have minimal impact on sleep, but heavier drinking (e.g. four–five drinks) may have a clinically significant impact (16–25‐min increase in sleep‐onset latency). Future studies may assess alcohol use as a point of intervention within this population.     

Persistent increased immunoglobulin M in treated narcotic addition. Association with liver disease and continuing heroin use

The increased serum IgM in treated narcotic addiction was studied using quantitative radial diffusion techniques. Seventy per cent of 68 untreated heroin addicts had serum IgM levels above 880 mg. per deciliter, the upper limit of normal. Only 7 per cent of 15 abstinent patients had high serum IgM, while 36 or 33 per cent of 109 patients maintained on methadone for at least one year had high serum IgM levels. Fourteen of these 36 had known heroin use and 10 others abused other drugs including alcohol, whereas only 2 of the 73 methadone-maintained patients with normal serum IgM had known drug abuse. The association between positive urine spots for morphine and elevated serum IgM levels was significant (p < 0.01). There was a significant relationship between laboratory evidence of liver disease and increased serum IgM levels. Increased serum alkaline phosphatase correlated better (p < 0.01) than the serum glutamic oxaloacetic transaminase (SGOT) (p < 0.05) with high serum IgM levels in methadone-maintained patients. High serum IgM levels in treated addicts are associated with continuing drug abuse and/or with laboratory evidence of continuing mild liver disease.     

Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis

The main predictor of outcomes in herpes simplex virus (HSV) encephalitis (HSE) is the delay between hospital admission and initiation of acyclovir. In this study, factors associated with late initiation of acyclovir were identified. The study included adults from northern France whose cerebrospinal fluid (CSF) was positive for HSV by PCR. Late initiation of acyclovir was defined as a delay of >1 day from hospital admission. In total, 184 patients were retrospectively enrolled from January 1991 to December 2002. The median age was 60 years (range: 17–91), and 102 (55.4%) were male. Acyclovir was initiated >1 day after hospital admission in 68 patients (37.0%). According to multivariate analysis, independent risk factors for late initiation of acyclovir were severe underlying disease (Knaus score ≥C) (OR 4.1; 95% CI  1.5–11.7); alcohol abuse (OR 3.4; 95% CI  1.3–8.9); and a delay of >1 day from admission to first brain imaging (OR 8.4; 95% CI  3.9–18.0). In addition, univariate analysis suggested an association between a finding of <10 leukocytes/mm³ in CSF at admission (OR 2.5; 95% CI  0.7–5.8). These characteristics were found in 26 (14.1%), 23 (12.5%), 66 (35.9%) and 27 (14.7%) patients, respectively. One risk factor was identified in 109 (59.2%) patients, two in 29 (15.8%), and three in six (3.3%). Patients with HSE often present with severe underlying disease, chronic alcohol abuse, or atypical CSF findings, and such factors should not be allowed to delay diagnosis and administration of acyclovir.     

Clusters of alcohol use disorders diagnostic criteria and predictors of alcohol use after liver transplantation for alcoholic liver disease

BACKGROUND: Establishing the correct alcohol use disorder diagnosis is clinically relevant because several reports of post-transplant alcohol use suggest that a pre-transplant diagnosis of alcohol dependence (rather than abuse) predicts relapse to alcohol use. Numerous combinations of specific symptoms are possible to achieve diagnostic significance. OBJECTIVE: The authors hypothesized that there would be distinct clusters of liver transplant recipients who showed specific combinations of alcohol-related symptoms and that these clusters would be predictive of alcohol-abuse outcome after transplant. METHOD: A group of 120 ALD liver transplant recipients received the Structured Clinical Interview for DSM-IV (SCID) module for alcohol abuse/dependence, and a cluster analysis was performed. RESULTS: Within the clusters of those with alcohol dependence, cluster assignment did not predict those more likely to drink. However, those assigned to the alcohol abuse cluster were significantly less likely to drink than those with alcohol dependence. CONCLUSION: Results therefore suggest that the prognosis regarding continued abstinence posttransplant is much more positive for individuals with a diagnosis of abuse than for those who meet criteria for alcohol dependence.     

Selective Breeding for High and Low Alcohol Preference in Mice

High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, out-bred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water ad libitum for 30 days and were selected based on the alcohol (g/kg) consumed per day over the entire period. Food was available ad libitum. At S10, line means for alcohol consumption differed greatly, with consumption of over 12 g/kg per day in the HAP mice and less than 2 g/kg per day in the LAP mice. Realized heritability for bidirectional selection was approximately 0.2. Female mice consumed more alcohol than male mice. There were no differences between lines in alcohol elimination rate, nor were there line differences in intake of salt or quinine solutions. However, consumption of saccharin solutions was greater in HAP mice than LAP mice, consistent with previous findings of a genetic correlation between sweet preference and alcohol drinking. Because the mouse genome is relatively well characterized, these selected lines should prove a useful tool for assessment of the genetic basis of, and phenotypes that correlate with, alcohol drinking.