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Neuroadaptations of Cdk5 in cholinergic interneurons of the nucleus accumbens and prefrontal cortex of inbred alcohol-preferring rats following voluntary alcohol drinking.

BACKGROUND: Neurobiological studies have identified brain areas and related molecular mechanisms involved in alcohol abuse and dependence. Specific cell types in these brain areas and their role in alcohol-related behaviors, however, have not yet been identified. This study examined the involvement of cholinergic cells in inbred alcohol-preferring rats following 1 month of alcohol drinking. Cyclin-dependent kinase 5 (Cdk5) immunoreactivity (IR), a marker of neuronal plasticity, was examined in cholinergic neurons of the nucleus accumbens (NuAcc) and prefrontal cortex (PFC) and other brain areas implicated in alcohol drinking, using dual immunocytochemical (ICC) procedures. Single Cdk5 IR was also examined in several brain areas implicated in alcohol drinking. METHODS: The experimental group self-administered alcohol using a 2-bottle-choice test paradigm with unlimited access to 10% (v/v) alcohol and water for 23 h/d for 1 month. An average of 6 g/kg alcohol was consumed daily. Control animals received identical treatment, except that both bottles contained water. Rats were perfused and brain sections were processed for ICC procedures. RESULTS: Alcohol drinking resulted in a 51% increase in Cdk5 IR cholinergic interneurons in the shell NuAcc, while in the PFC there was a 51% decrease in the percent of Cdk5 IR cholinergic interneurons in the infralimbic region and a 46% decrease in Cdk5 IR cholinergic interneurons in the prelimbic region. Additionally, single Cdk5 IR revealed a 42% increase in the central nucleus of the amygdala (CNA). CONCLUSIONS: This study identified Cdk5 neuroadaptation in cholinergic interneurons of the NuAcc and PFC and in other neurons of the CNA following 1 month of alcohol drinking. These findings contribute to our understanding of the cellular and molecular basis of alcohol drinking and toward the development of improved region and cell-specific pharmacotherapeutic and behavioral treatment programs for alcohol abuse and alcoholism.

Adaptation, Physiological↗

Social and psychologic correlates of problem drinking in old age.

A study of the drinking behavior of 928 noninstitutional residents of Boston, aged 60 or older, showed that 53 per cent drinks; and 6 per cent, two or more drinks. Nine subjects (1 per cent) were self-reported problem drinkers, and another 31 (3 per cent) reported that drinking had diminished the quality of their lives. Problem drinkers and those with alcohol-related problems were likely to be young-old native-born men. They were less likely to be satisfied with their relationships with family members, spouses, and close friends. All problem drinkers had long-term drinking problems. Most had sought treatment, but only one was being treated at the time of the study. The data suggest that current theories do not adequately explain late-life problem drinking and that current initiatives do not adequately address the needs of the elderly population at large.

Adolescent↗

Drinking habits among older persons: findings from the NHANES I Epidemiologic Followup Study (1982-84). National Health and Nutrition Examination Survey.

OBJECTIVES: To describe alcohol use and its sociodemographic correlates among persons aged 65 years and older in a US probability sample. DESIGN: Cross-sectional analysis of a national probability sample-based cohort study. SETTING: Multiple sites throughout the United States. PARTICIPANTS: A total of 3448 persons aged 65 and older who participated in the first wave of the NHANES I Epidemiologic Followup Study (1982-84). MEASUREMENTS: We describe the alcohol use behaviors and demographic characteristics of 3448 persons aged 65 and older. Least squares regression models were used to assess associations between older persons' sociodemographic characteristics and alcohol use. RESULTS: Sixty percent of the sample reported having 12 or more drinks of alcohol in at least 1 year of their lives. Seventy-nine percent of these older drinkers were currently drinking. Twenty-five percent of all drinkers drank daily (31% men, 19% women). Using gender-specific definitions (men >2 drinks/day; women >1 drink/day), 16% of men drinking alcohol and 15% of women drinking alcohol were heavy drinkers. Younger age, male gender, and higher income were associated with greater alcohol use. CONCLUSIONS: Most older persons who ever drank alcohol in their lifetimes were currently drinking. In addition, a substantial number of older persons were drinking currently at levels that may place them at risk of adverse health consequences.

Age Distribution↗

The role of heavy drinking in the risk of traffic fatalities.

Recent studies have identified a "hard core" of drinking drivers who do not fit a "social" drinker profile and may require medical intervention. This article builds on these studies by quantifying the role of heavy drinking in motor vehicle fatalities. Data on male alcohol-involved fatally injured drivers (AIFIDs) were obtained from the U.S. Fatal Accident Reporting System (FARS) for the years 1989-1990 (n = 8876). The AIFIDs were grouped into either a "heavy" or "light" drinking category based on drinking behaviors inferred from prior driving records and blood alcohol concentrations (BAC). The majority of male AIFIDs were between the ages of 20-39 (70%). Sixty-five percent had a BAC of 150 mg/dl or greater, and 41% had a BAC in excess of 200 mg/dl. AIFIDs with high BACs were more likely to have histories of DUI convictions and license suspensions than AIFIDs with low BACs. According to the study's criteria, 73% percent of the AIFIDs could be classified as "heavy" drinkers. There were no driving variables that differentiated the heavy and light drinker groups, indicating that heavy drinking per se is the primary factor that distinguishes the groups. Male alcohol-involved fatally injured drivers are comprised mostly of heavy drinkers who may suffer from serious drinking problems or alcoholism. Successful interventions may require medical treatment as well as punitive criminal justice policies.

Accidents, Traffic↗

Injury as a motivator to reduce drinking.

OBJECTIVES: To identify predictors of readiness to change drinking behavior by minor-injury patients who had positive saliva alcohol tests (SATs) in the ED. To develop and test a model intended to be prognostic of readiness to change, which included predispositional and injury-event-related variables. METHODS: An on-site survey was conducted of minor-injury ED patients sampled consecutively during predesignated periods. Patients were identified as SAT-positive during their screening evaluations. After giving their consent, they were administered a self-report battery that assessed predispositional and injury-event-related variables as well as readiness to change their drinking. Predictors of readiness to change drinking were tested with regression analyses. RESULTS: Twenty-four SAT-positive patients participated; there were 18 men and six women (average age 34 years). Preinjury predispositional variables were by themselves unrelated to the patient's readiness to change while in the ED. Aversiveness of the injury and perception of degree of alcohol involvement were injury-event-related variables predictive of readiness to change (p < 0.008). Negative consequences attributed to drinking prior to the injury event strengthened the association of injury aversiveness and alcohol involvement with readiness to change (p < 0.0075). CONCLUSION: Interventions to decrease drinking in this population should focus on increasing patient awareness of the association between drinking, injuries, and other alcohol-related negative consequences.

Adult↗

Sex differences in problem drinking among 42-year-old residents of Malmö, Sweden.

The main objective was to describe sex-related differences in rates of nonidentified vs identified problem drinking in 42-year-old Malmö residents. All 1264 women and 1368 men born in 1941 were invited to a health screening at the Preventive Medicine Section, Malmö General Hospital. Individuals registered at the Department of Alcohol Diseases because of problem drinking prior to screening (identified problem drinkers) were excluded and analyzed separately. Intervention in the remaining subjects was made if any of 3 sets of inclusion criteria was met. The sex ratios (female:male) of identified and nonidentified problem drinking were 1:4.1 and 1:2.8 respectively. Thus, nonidentified problem drinking is by and large proportional to identified problem drinking in both sexes, arguing against hidden drinking being and exclusively female phenomenon.

Alcohol Drinking↗

Influence of drinking method on tooth-surface pH in relation to dental erosion.

The aim of this investigation was to study the intraoral pH response on tooth surfaces in relation to dental erosion during and after drinking a sugar-free cola-type soft drink. Six different methods of drinking were tested in a randomized order: holding; short-sipping; long-sipping; gulping; nipping; and sucking. Two methods of pH measurement were used in two series of individuals. In the first series, pH was measured by using the microtouch method in 12 healthy adults at three dental erosion-prone sites: 11 palatally; 11 buccally; and at the mesiobuccal cusp tip of 16. In the second series, pH was measured by using the telemetric method in 6 healthy individuals, producing continuous recordings of pH by means of a glass electrode in a specified approximal area. The two series showed similar results, although the telemetric method generally recorded larger pH falls. Holding the drink in the mouth before swallowing led to the most pronounced pH drop, followed by the long-sipping method. Gulping resulted in only a small decrease of pH. No differences among the three intraoral sites were found when analyzed by using the microtouch method. The conclusion from this study is that the drinking method strongly affects tooth-surface pH and thereby the risk for dental erosion. It therefore seems appropriate to include advice on the method of drinking in dietary counseling related to dental erosion.

Adolescent↗

Adolescent gender differences in alcohol problem behaviors and the social contexts of drinking.

This study of more than 1,300 high school students examined gender differences in the social context of drinking associated with four alcohol problem behaviors (high intensity drinking, binge drinking, driving while intoxicated, and riding with an alcohol impaired driver). A series of analyses treated five social contexts of drinking (Social Facilitation, School Defiance, Stress Control, Peer Acceptance, and Parental Approval) as dependent variables and revealed significant multivariate interaction effects between gender and all four alcohol problem behaviors. Male problem drinkers were more likely to drink in all social contexts than female problem drinkers or non-problem drinkers of both genders. Females were no more likely to drink in the context of Stress Control than males, a finding inconsistent with some previous research. The social contexts of Social Facilitation, School Defiance, and Stress Control were the best discriminators of problem versus non-problem drinkers of both genders (although the order of importance varied by gender and specific problem behavior). Implications for designing targeted interventions are discussed.

Adolescent↗

Factors in adolescent drinking/driving: binge drinking, cigarette smoking, and gender.

During three consecutive years, 3,137 high school seniors from three graduating classes in one Michigan county were surveyed. The primarily White sample reported their use of alcohol and cigarettes, driving experience, and drinking/driving experience. Survey data were linked with state driver history records. Fully one-third of the high school seniors reported driving after drinking in the past six months. To identify factors associated with self-reported drinking/driving, correlation and regression analyses were conducted. Frequent binge drinking and riding with a drinking driver were consistent factors in driving after drinking frequency. Being male, smoking cigarettes, having frequent use of a motor vehicle, having a driving offense on record, and number of years licensed were important correlates, varying by year of graduation. Comprehensive interventions to moderate drinking, smoking, and driving after drinking are needed.

Adolescent↗

Oro-gastro-intestinal inhibition of hypernatremia-induced drinking in the goat.

Reduction of drinking by slow (5 ml/min) administration for 20 min of nearly body-warm (35 degrees C) and cold (15 degrees C) water into the mouth, the abomasum, or the duodenal bulb was studied in goats made thirsty by the simultaneous i.v. infusion of hypertonic (2 M) NaCl at 2 ml/min. During the control experiments the drinking response to corresponding infusion of 1.7 M NaCl was recorded. This in order to eliminate the possible influence on the results of a postabsorptive thirst inhibition which would occur if the administered water was completely absorbed already during the saline infusion. The entrance of warm water into the mouth or into the abomasum caused about 20%, and into the duodenal bulb about 30% reduction of drinking during the infusion of hypertonic NaCl. The corresponding reduction for cold water was when introduced into the mouth and duodenal bulb about 50% and into the abomasum about 60%. Cold water also considerably delayed the onset of drinking. The inhibition obtained during cold water administration was partially compensated for by increased post-infusional drinking. As regards the sensory input underlying preabsorptive inhibition of thirst, it is concluded that (regardless of distension, swallowing, and other mechanical factors) the entrance of pure water into various parts of the alimentary tract contributes to reduce the thirst drive. In addition, stimulation of oral, gastric, and duodenal cold receptors obviously diminish the urge to drink considerably.

Animals↗

Drinking and antidiuresis elicited by isoprenaline in the dog.

1. Isoprenaline hydrochloride injected subcutaneously or infused intravenously caused drinking and simultaneous antidiuresis in the dog. The minimal effective dose was between 20 and 50 mug per dog.2. Isoprenaline-induced drinking was prevented by the beta-adrenergic antagonist propranolol and enhanced by the alpha-antagonist phentolamine.3. Ganglionic blockade with pentolinium or with hexamethonium did not interfere with the response.4. A delay of 1 hr after injection of 100 mug isoprenaline, before drinking was permitted, did not significantly reduce the amount of water subsequently drunk. A preload of water approximately equal to the volume of water normally drunk caused a greater reduction in water intake in some dogs.5. Isoprenaline caused an increase in heart rate and pulse pressure which lasted for between 1 and 3 hr according to dose. Central venous pressure fell, but mean arterial pressure was little altered. Haemodynamic changes preceded drinking by about 5 min.6. Infusion of isoprenaline caused drinking in the bilaterally nephrectomized dog.7. We conclude that isoprenaline is a potent stimulus to drinking in the dog and that the effect is not exclusively mediated by the renin-angiotensin system.

Animals↗

Hepatic portal vein infusion of glucose and sodium solutions on the control of saline drinking in the rat.

1. Rats were prepared under anaesthesia with non-occlusive catheters in hepatic portal vein (HP) and inferior vena cava (VC) and maintained under standard conditions. 2. Each rat received a series (3 day intervals) of 30 min infusions of different solutions or sham into HP or VC. Oral intake of 0.15 M-NaCl and water were measured for 30 min. Significant change in drinking behaviour was assumed when the response to HP infusion differed from both sham and VC infusion. 3. Saline drinking was inhibited by HP infusion of 1 M- or 2M-NaCl, an effect blocked by right vagotomy or by addition of 16 mM-KCl to the infusate. 4. Saline drinking was increased and water drinking decreased by HP infusion of 2 M-glucose but not sucrose or fructose. 5. Saline drinking was decreased by HP infusion of deoxy-D-glucose to inhibit glucose utilization or ouabain to inhibit (Na4-K+) ATPase. 6. Results are consistent with the presence of afferent nerve terminals in hepatic portal vessels which are sensitive to change in NaCl or glucose concentration and which, in response thereto, alter drinking behaviour. The effects of NaCl and glucose on the discharge rate of the nerve terminals may be interpreted in terms of changing activity or electrogenicity of a Na pump but changes in membrane conductance or Na influx cannot be ruled out.

Animals↗

Drinking and haemodynamic changes induced in the dog by intracranial injection of components of the renin-angiotensin system.

1. Intracranial injections of the individual components of the renin-angiotensin system caused drinking in water-replete dogs. 2. Angiotensin II was the most reliable, potent and rapidly acting intracranial dipsogen and elicited drinking in the absence of peripheral circulatory changes. After the highest dose of angiotensin II (10(-9) mole) five dogs drank a mean amount of 380.0 +/- 88.6 ml. For the other components, the order of dipsogenic effectiveness was angiotensin I, synthetic renin substrate, and angiotensin III. 3. Isotonic saline, bradykinin (10(-10) mole), eledosin-hexapeptide (10(-10) mole), oxytocin (10(-10) mole) and prostaglandin F2alpha (1-200 X 10(-12) mole) were ineffective. 4. Intracranial renin (10 m-u.) produced a mean intake of 445 +/- 152 ml. of water in eight dogs. 5. Dog renin substrate and synthetic renin substrate, injected intracranially in a dose of 10(-10) mole, produced similar intakes of water but these amounts were very much less than the volume drunk in response to the same dose of angiotensin II. 6. None of the components injected into dipsogenically responsive sites in the brain caused changes in blood pressure, although the act of drinking itself produced a small rise. 7. Angiotensin II at the highest dose produced drinking when injected into the subfornical organ, preoptic region, anterior hypothalamus, lateral ventricle, third ventricle, ventral hippocampus and mid-line thalamus. Negative sites were found in the caudate nucleus, fourth ventricle, mid-brain, posterior thalamus, dorsal hippocampus, lateral hypothalamus and posterior hypothalamus. 8. After the lowest dose of intracranial angiotensin II (10(-12) mole) only the preoptic region and subfornical orgal were responsive. These two sites were equally sensitive in terms of latency and amounts drunk at all doses injected. 9. Angiotensin did not necessarily have to reach a cerebral ventricle in order to cause drinking. 10. The dog resembles the rat in its responsiveness to the dipsogenic action of intracranial angiotensin II. The regions of the brain from which drinking can be elicited are more widespread than has been claimed by some in the rat.

Angiotensinogen↗

Transient cutaneous vasodilatation and hypotension after drinking in dehydrated and exercising men.

We examined whether oropharyngeal stimulation by drinking released the dehydration-induced suppression of cutaneous vasodilatation and decreased mean arterial pressure (MAP) in exercising subjects, and assessed the effects of hypovolaemia or hyperosmolality alone on these responses. Seven young males underwent four hydration conditions. These were two normal plasma volume (PV) trials: normal plasma osmolality (P(osmol), control trial) and hyperosmolality (DeltaP(osmol) = +11 mosmol (kg H(2)O)(-1)); and two low PV trials: isosmolality (DeltaPV = -310 ml) and hyperosmolality (DeltaPV = -345 ml; DeltaP(osmol) = +9 mosmol (kg H(2)O)(-1)), attained by combined treatment with furosemide (frusemide), hypertonic saline and/or 24 h water restriction. In each trial, the subjects exercised at 60% peak aerobic power for approximately 50 min at 30 degrees C atmospheric temperature and 50% relative humidity. When oesophageal temperature (T(oes)) reached a plateau after approximately 30 min of exercise, the subjects drank 200 ml water at 37.5 degrees C within a minute. Before drinking, forearm vascular conductance (FVC), calculated as forearm blood flow divided by MAP, was lowered by 20-40% in hypovolaemia, hyperosmolality, or both, compared with that in the control trial, despite increased T(oes). After drinking, FVC increased by approximately 20% compared with that before drinking (P < 0.05) in both hyperosmotic trials, but it was greater in normovolaemia than in hypovolaemia (P < 0.05). However, no increases occurred in either isosmotic trial. MAP fell by 4-8 mmHg in both hyperosmotic trials (P < 0.05) after drinking, but more rapidly in normovolaemia than in hypovolaemia. PV and P(osmol) did not change during this period. Thus, oropharyngeal stimulation by drinking released the dehydration-induced suppression of cutaneous vasodilatation and reduced MAP during exercise, and this was accelerated when PV was restored.

Blood Pressure↗

Doctors' drinking habits and consumption of alcohol.

Alcohol consumption and drinking habits among Finnish doctors were studied as part of a survey of stress and burnout. A questionnaire containing 99 questions or groups of questions was sent to all 3496 practising doctors aged under 66 randomly selected from the registry of the Finnish Medical Association. Altogether 2671 doctors (76%) responded; this sample was representative of the Finnish medical profession. The average weekly consumption of alcohol during the past year and various aspects of drinking behaviour were assessed, and the presence or absence of symptoms and diseases often encountered among heavy drinkers and addicts was determined. The data were analysed separately for men and women, for those aged less than or equal to 40 and greater than 40, and for the men with high and low alcohol consumption and with high and low scores on the index of drinking habits. Selected variables related to work, stress, and coping were correlated with alcohol consumption and drinking behaviour. The median consumption of alcohol among male doctors was 4876 g (6.2 litres) and among female doctors 2226 g (2.8 litres) of absolute alcohol per person per year and was higher in those aged over 40. Beer was most commonly drunk by men and wine by women. Increased alcohol consumption was associated with older age, disappointment with career, heavy smoking, use of benzodiazepines, stress and burnout symptoms, suicidal thoughts, general dissatisfaction, and diseases related to alcohol. Drinking habits were heavier among doctors working in community health centres, those taking long sick leaves, younger doctors disappointed with their careers or the atmosphere at work, and older doctors immersed in their work. Alcohol consumption among doctors seems to be higher than that of the general population in Finland, and heavy drinking seems to be associated with stress and burnout.

Adult↗

Stopping drinking and risk of oesophageal cancer.

OBJECTIVE: To examine the effect of stopping drinking on the risk of oesophageal cancer. DESIGN: Hospital based case-control study. SETTING: Surgical departments of four district general hospitals and general practices in Hong Kong. SUBJECTS: Cases were 400 consecutive admissions of patients with histologically confirmed diagnosis of oesophageal cancer during a 21 month period in 1989-90 (87% response rate). Controls were 1598 patients selected from the same surgical departments as the cases and from the general practices from which the cases were originally referred (95% response rate). MAIN OUTCOME MEASURE: Relative risk of developing oesophageal cancer after stopping drinking (adjusted for age, education, place of birth, smoking, and diet). RESULTS: Current light drinking (< 200g ethanol/week) was not associated with significant increase in risk. Among former drinkers risk fell more quickly in moderate (200-599 g/week) than heavy (> or = 600 g/week) drinkers. Even among heavy drinkers, however, risk had dropped substantially after five to nine years of not drinking. The results suggest that the time taken for risk to return to that in subjects who never drink was 10-14 years for moderate drinkers and 15 years or more, if ever, for heavy drinkers. CONCLUSION: Risk of oesophageal cancer decreases fairly rapidly with time after abstaining from drinking. This new finding could be used in health promotion to encourage behavioural changes, especially in heavy drinkers, who have a very high risk of developing oesophageal cancer. It also suggests that alcoholic beverages have a strong effect on the late stage of carcinogenesis.

Adenocarcinoma↗

Prospective study of alcohol drinking patterns and coronary heart disease in women and men.

OBJECTIVE: To determine the association between alcohol drinking patterns and risk of coronary heart disease in women and men. DESIGN: Population based cohort study. SETTING: Denmark, 1993-2002. PARTICIPANTS: 28 448 women and 25 052 men aged 50-65 years, who were free of cardiovascular disease at entry to the study. MAIN OUTCOME MEASURES: Incidence of coronary heart disease occurring during a median follow-up period of 5.7 years. RESULTS: 749 and 1283 coronary heart disease events occurred among women and men. Women who drank alcohol on at least one day a week had a lower risk of coronary heart disease than women who drank alcohol on less than one day a week. Little difference was found, however, between drinking frequency: one day a week (hazard ratio 0.64, 95% confidence interval 0.51 to 0.81), 2-4 days a week (0.63, 0.52 to 0.77), five or six days a week (0.79, 0.61 to 1.03), and seven days a week (0.65, 0.51 to 0.84). For men an inverse association was found between drinking frequency and risk of coronary heart disease across the entire range of drinking frequencies. The lowest risk was observed among men who drank daily (0.59, 0.48 to 0.71) compared with men who drank alcohol on less than one day a week. CONCLUSIONS: Among women alcohol intake may be the primary determinant of the inverse association between drinking alcohol and risk of coronary heart disease whereas among men, drinking frequency, not alcohol intake, seems more important.

Aged↗

Factors affecting thermogenic drinking in rats.

After as little as 6 h of exposure to cold air, drinking was induced in rats following transfer from air at 5 degreesC to air at 26 degreesC. Drinking began within 15 min after transfer from the cold enviroment and lasted approximately 1 h. The stimulus for initiation of drinking was most likely the temperature change resulting from the transfer, since an ambient temperature difference of 10 centigrade degrees or more was required to initiate a drinking response after transfer from air at 5 degreesC. Thermogenic drinking was not thwarted by preventing access to water for either 1 or 2h following transfer to warm air, but either intragastric or intraperitoneal administration of a water load equal to 3% of body weight inhibited water intake following transfer.The characteristics of the drinking response following transfer than 5 to 26 degrees C were similiar to those observed following 24 h of dehydration at 26 degrees C. Thus, the cold-exposed rat is relatively dehydrated compared with controls.

Animals↗