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PubMed2003

Risperidone reduces limited access alcohol drinking in alcohol-preferring rats.

An atypical antipsychotic drug risperidone reduced ethanol drinking of ethanol-preferring Alko, Alcohol (AA) rats in a limited access paradigm. Its effect was transient at a dose known to preferentially antagonize the 5-HT(2) receptors (0.1 mg/kg, s.c.), but long-lasting when the dose was increased to 1.0 mg/kg that also blocks dopamine D(2) receptors. Risperidone also reduced dose-dependently locomotor activity and limited access saccharin intake of the AA rats, indicating that its effect on ethanol drinking was not selective. Risperidone at 0.1 mg/kg given before four successive daily ethanol-drinking sessions significantly reduced the ethanol intake. These data from an animal model of high ethanol intake suggest that risperidone should be tested in various populations of alcoholics for reducing ethanol consumption.

Alcohol Drinking↗
PubMed2004

Relationship between alcohol drinking and alcohol-related health problems.

OBJECTIVE: To study the relationship between drinking environment, attitudes and situation and alcohol-related health problems. METHODS: A sample of 2327 respondents was randomly collected from Wuhan, Hubei Province in China by a face-to-face interview. The structural equation modeling analysis was performed for the data collected. RESULTS: Both parents' drinking behaviors and respondents' drinking situation strongly impacted the alcohol-related problems and diseases. Friends' or peers' drinking behaviors influenced the respondents' drinking attitudes and behaviors. Males experienced more alcohol-related problems and diseases than females. CONCLUSIONS: Comparatively, parents' drinking behaviors exert the most significant influence on drinkers. Therefore, it is beneficial to restrict parents' drinking behaviors for the offsprings and the whole society, and an intensive professional education in early motherhood is also necessary for Chinese women.

Adolescent↗
PubMed1996

Low Km aldehyde dehydrogenase (ALDH2) polymorphism, alcohol-drinking behavior, and chromosome alterations in peripheral lymphocytes.

Excessive drinking of alcohol is now widely known to be one of the major lifestyle choices that ca effect health. Among the various effects of alcohol drinking, cytogenetic and other genotoxic effects are of major concern from the viewpoint of prevention of alcohol-related diseases. Alcohol is first metabolized to acetaldehyde, which directly causes various types of chromosomal DNA lesions and alcohol-related diseases, and is then further detoxified to the much less toxic metabolite acetate. About 50% of Oriental people are deficient in the aldehyde-dehydrogenase 2 isozyme (ALDH2) that can most efficiently detoxify acetaldehyde. We have performed a series of experiments to investigate how the genetic deficiency in ALDH2 affects the behavioral pattern for alcohol drinking and the sensitivity of peripheral lymphocytes to the induction of chromosome alterations by exposure to alcohol and alcohol-related chemicals. We found great effects of the ALDH2 genotypes on alcohol sensitivity and alcohol-drinking behavior. We also show that lymphocytes from habitual drinkers with the deficient ALDH2 enzyme had significantly higher frequencies of sister chromatid exchanges than those from ALDH2-proficient individuals.

Adult↗
PubMed1988

Characteristics of ethanol tolerance in alcohol drinking (AA) and alcohol avoiding (ANA) rats.

The development of tolerance to ethanol was examined in two rat lines selected for high (AA) and low (ANA) ethanol consumption. In the first experiment, the acquisition of tolerance to the motor-impairment, hypothermic and hypnotic effects of ethanol produced by daily treatment with 5 g/kg ethanol for a period of 24 days was examined. Tolerance to these effects of ethanol was observed in the AA rats while marginal or no tolerance was demonstrated in the ANA rats. In the second experiment the development of rapid tolerance to the hypothermic and hypnotic effects of ethanol was examined. The hypothermic and hypnotic responses to IP injection of 3.5 g/kg ethanol were found to be attenuated in the AA but not the ANA rats by a single equivalent ethanol injection given 24 h earlier. These results suggest some relationship between the capacity to develop tolerance and voluntary ethanol intake.

Alcohol Drinking↗
PubMed1982

Effects of intravenous ethanol and of 4-methylpyrazole on alcohol drinking in alcohol-preferring rats.

Studies were undertaken to determine if elevated blood alcohol concentrations (BAC), produced by intravenous (IV) infusion of ethanol or by intraperitoneal (IP) administration of 4-methylpyrazole (4-MP), could reduce the free-choice oral alcohol consumption of adult male alcohol-preferring rats (P-rats). The IV infusion of ethanol either on a 24 or 12 (dark) hourly dose schedule reduced the amount of ethanol voluntarily ingested. There was a significant (p less than 0.05) inverse correlation between the amount of ethanol consumed orally and the amount of ethanol infused. Daily fluid and caloric intakes were not compromised. When the amount of ethanol infused was 85% or more of the control oral intake, there was a significant correlation between ethanol intake and tail-blood alcohol levels, taken at 5 min (r = 0.98; p less than 0.05) and 55 min (r = 0.93, p less than 0.05) after the last dark cycle infusion. Below the preinfusion level of 85%, the BAC were variable and did not correlate well with total ethanol intake. After a single IP injection of 4-MP, 90 mg/kg body wt, BAC increased from 10 mg% to 50-65 mg% for 2-3 days. Concomitant with the rise in BAC, these animals decreased their drinking of 10% ethanol and proportionately increased their water intake. The present studies suggest that pharmacological factors, distinct from orosensory cues, are important in regulating voluntary ethanol drinking behavior in the P-rats.

Alcohol Drinking↗
PubMed1988

Influence of several factors on blood alcohol concentrations after drinking alcohol.

The influence of several factors on the blood alcohol course after drinking diluted ethanol was studied in young, healthy volunteers under strictly standardized conditions. These factors were sex, dose and concentration of the alcohol, physical exercise immediately after drinking, meal consumption before drinking and energy content and composition of the meal. In 18 blood samples, taken within 6 hr after alcohol ingestion, blood alcohol concentration (BAC) was determined enzymatically. Concomitantly breath analyses were performed. In general, both methods gave similar results. Peak concentration and area under the blood alcohol curve increased with increasing dose. With the same amount of ethanol, peak concentration and area under the curve tended to be greater in women than in men. Consumption of a meal had an attenuating effect. The area under the curve was smaller after a high-energy meal than after a low-energy meal. Peak concentration depended on meal composition, increasing in the order high protein less than high sucrose = high complex carbohydrate less than high fat. A similar trend was observed for the area under the blood alcohol curve.

Adult↗
PubMed1998

More vasopressin mRNA in the paraventricular hypothalamic nucleus of alcohol-preferring rats and high alcohol-drinking rats selectively bred for high alcohol preference.

Both the selectively bred alcohol-preferring (P) and high alcohol-drinking (HAD) rats exhibit alcohol preference, and develop tolerance to alcohol more quickly than their counterparts, the alcohol-nonpreferring (NP) and low alcohol-drinking (LAD) rats, respectively. It has been shown that the P rats retain developed tolerance longer than do NP rats, and alcohol drinking increases concurrently with the development of tolerance. Although alcohol preference and tolerance are fundamental elements of alcoholism, the exact mechanisms underlying these two phenotypes in P and HAD rats are not well understood. Recent studies have suggested that arginine vasopressin (AVP) may be involved in modulation of alcohol tolerance. Accordingly, this study was designed to examine whether the AVP mRNA level in the hypothalamus differs in rats that have been selectively bred for alcohol preference and nonpreference. A 35S-AVP antisense oligodeoxynucleotide probe was used for in situ hybridization to localize AVP mRNA in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), two major sites for AVP synthesis in the hypothalamus. Quantitative autoradiography demonstrated that P rats had higher levels of AVP mRNA in the PVN than NP rats. Similarly, higher levels of AVP mRNA were also found in the PVN of HAD rats, compared with LAD rats. The AVP mRNA levels in the SON were similar in the alcohol-preferring and alcohol-nonpreferring rat lines. Basal plasma AVP levels were higher in NP rats than in P rats as determined by radioimmunoassay, whereas plasma AVP levels were not significantly different between HAD and LAD rats. The results suggest that increased AVP gene expression in the PVN may contribute to alcohol preference and the development of alcohol tolerance.

Alcohol Drinking↗
PubMedDate not supplied

Opiate and 5-HT2A receptors in alcohol drinking: preference in HAD rats is inhibited by combination treatment with naltrexone and amperozide.

Amperozide, a 5-HT2A receptor antagonist, and naltrexone, an opiate receptor antagonist, have been shown to suppress volitional drinking of alcohol in experimental animals. The present study examined the effects of the concurrent administration of both drugs on the volitional intake of alcohol in the selectively bred, high alcohol drinking (HAD) rat. Individual preferences for alcohol were determined by a standard 10-day test in which alcohol concentrations were increased from 3% to 30%. Following a 4-day predrug test during which water together with a maximally preferred concentration of 7% to 20% was offered to each HAD rat, amperozide and naltrexone were injected SC over a second 4-day period as follows: 1) amperozide at 1600 h and naltrexone at 2200 h; 2) the same drugs but in reversed temporal order; and 3) amperozide and naltrexone administered simultaneously at 1600 and 2200 h. Thereafter, alcohol preference testing continued for a third 4-day period. The alternate delivery of both drugs attenuated significantly the absolute g/kg and proportional intakes of alcohol in the HAD rats, whereas the saline vehicle was without effect. Although the simultaneous administration of naltrexone and amperozide produced an even greater decline in alcohol intake, without side effects on food and water intakes or on body weight, some residual drinking of alcohol persisted. Nevertheless, the results corroborate our previous findings on the suppression of alcohol drinking by antagonists of opiate and 5-HT2A receptors. Because amperozide and naltrexone together reduce the apparent reinforcing property of alcohol, the theory is supported that the addictive liability to alcohol is underpined by multiple receptor subtypes within the mesolimbic and other systems in the brain.

Alcohol Drinking↗
PubMed2006

Alcohol drinking habits and community perspectives on alcohol abuse in the Bella Coola Valley.

INTRODUCTION: This study surveyed the residents of the rural and remote communities in the Bella Coola Valley, British Columbia, on their alcohol drinking habits and on their opinions as to which of a list of health issues were the most important considerations for the well-being of the community. METHODS: People aged 17 years and older living in the Bella Coola Valley were asked to complete a detailed Health and Quality of Life Survey during the period August 2001 to May 2002. This included two separate mailouts. Alcohol drinking habits; and ratings on whether or not people believed that alcohol abuse, drug abuse, family violence, unemployment, sexual abuse and racial discrimination were surveyed. RESULTS: A total of 674 adults age 17 years and older (39% response rate) completed an 11-page questionnaire. Results from the survey indicate that unemployment, alcohol abuse and drug abuse are seen as the most important community health problems by the majority of residents. Eighty-eight percent of respondents agree or strongly agree that unemployment is a problem; for alcohol abuse it was 83%, for drug abuse 77%, for both family violence and sexual abuse 58%, and for racial discrimination it was 53%. Patterns of drinking habits vary considerably between Aboriginal peoples and non-Aboriginal people. More Aboriginal respondents abstained from drinking alcoholic beverages (54%) than non-Aboriginal respondents (22%). Among the Aboriginal peoples who did drink alcohol, there were relatively more heavy drinkers (36%) compared with non-Aboriginal people (7%). There were more heavy drinkers among men than among women. CONCLUSION: Patterns of drinking habits vary between men and women and between Aboriginal and non-Aboriginal people. The majority of residents agree that alcohol is a problem in these communities. Unemployment, drug abuse, family violence, sexual abuse and racial discrimination are also believed to be important issues for the Bella Coola Valley. This information should be used to set priorities for future health and wellness programs.

Adolescent↗
PubMed2003

The age of drinking onset and housing condition influences rat alcohol drinking behavior.

We investigated whether age of drinking onset and/or the housing condition in experimental animals affected alcohol drinking behavior to extrapolate the experimental findings to alcohol drinking patterns of aged people. At the time of the experiments, all 1-, 4-, 10- and the 16-month-old rats were divided into two groups, isolated and aggregated groups, and then maintained in the same housing conditions for six months. The amounts of voluntary alcohol consumption (g/kg/day) of all rats were investigated by two-bottle methods at 7, 10, 16 and 22 months old. No significant difference in alcohol drinking behavior was shown in the 7- and 10-month-old rats. A decrease in voluntary alcohol consumption was shown in the 16-month-old rats of the aggregated groups. In the 22-month old rats, a significant suppression of voluntary alcohol consumption was found in the aggregated groups compared with the isolated group. The results demonstrate that an important determinant of EtOH intake is related to environmental factors. It was suggested that alcohol drinking behavior strongly depends on the housing conditions and the age of onset of alcohol drinking.

Age Factors↗
PubMed2004

Clozapine reduces alcohol drinking in Syrian golden hamsters.

Alcohol abuse contributes substantially to the overall morbidity of schizophrenia. While typical antipsychotic medications do not limit alcohol use in patients with schizophrenia, emerging data suggest that the atypical antipsychotic clozapine does. To further elucidate the effects of these antipsychotics on alcohol use, we initiated a study in alcohol-preferring rodents. Syrian golden hamsters were given free-choice, unlimited access to alcohol. Nine days of treatment (s.c. injection) with clozapine (2-4 mg/kg/day), but not haloperidol (0.2-0.4 mg/kg/day), reduced alcohol drinking. Clozapine reduced alcohol drinking by 88% (from 11.3+/-1.7 to 1.4+/-0.2 g/kg/day) while increasing both water and food intake. Alcohol drinking gradually (during 24 days) returned toward baseline in the clozapine-treated animals when vehicle was substituted for clozapine. Further increasing the doses of haloperidol (0.6-1.0 mg/kg/day) had no effect on alcohol drinking; moreover, very low doses of haloperidol (0.025-0.1 mg/kg/day) tested in separate groups of hamsters also had no effect on alcohol drinking. This study demonstrates that clozapine, but not haloperidol, can effectively and reversibly decrease alcohol consumption in alcohol-preferring hamsters. The results are compatible with the observations that clozapine, but not haloperidol, limits alcohol use in patients with schizophrenia. These data further suggest that clozapine may serve as a prototype for developing novel treatments for alcohol abuse.

Alcohol Drinking↗
PubMed1995

[Relation between the quantity, type and duration of alcohol drinking and the development of alcoholic liver cirrhosis].

Patients with alcoholic liver cirrhosis in Dalmatian region are presented in this paper and their social and medical characteristics are reviewed. The alcohol drinking habits of 211 patients with established clinical-laboratory criteria of alcoholic liver cirrhosis were investigated. The obtained results have been compared with the results of the control group. The average age of the patients was 51.6 years. Males were more numerous (2/3 of all examinees), while the average duration of alcohol consumption was 25.4 years. Wine was the most frequently consumed beverage (about 90% of cases) and the average daily intake was 151 g of pure alcohol. The authors prove by mathematical model that the occurrence of liver cirrhosis increases exponentially with the increase of the amount of alcohol consumed. Relative risk of the development of alcoholic liver cirrhosis increases many fold with the increase of the amount of alcohol consumed.

Alcohol Drinking↗
PubMed2002

Videotaped cue for urge to drink alcohol.

BACKGROUND: The urge to drink alcohol can be robustly and reliably induced via actual exposure to a person's preferred alcoholic beverage. Unfortunately, these exposure paradigms are unwieldy for functional magnetic resonance imaging studies. The goal of this study was to examine whether viewing a personalized videotaped cue could induce alcohol craving. The following hypotheses were tested: (1) individualized cue videotapes can reliably elicit the urge to drink alcohol in alcohol-dependent participants and (2) alcohol drinking histories can predict reactivity to cue. METHODS: DSM-IV criteria were used to identify an alcohol-dependent group (ADG). Controls included a light-drinking group and a moderate-drinking group. Urge to drink alcohol was assessed at baseline and after each of five in vivo exposure conditions: water (W), alcohol 1 (A1), mood induction (M), alcohol 2 (A2), and relaxation (R). The entire exposure session was videotaped. Each participant's video footage was digitally edited to produce a 17.5-min cue that was presented to the participant 24 to 72 hr later. Ratings of urge to drink alcohol across the five exposure conditions were compared for both the in vivo and the video exposure sessions. RESULTS: Fourteen participants (five in the light-drinking group, four in the moderate-drinking group, and five in the ADG) completed both sessions. Participants in each group showed differences between neutral cue exposure (W and R) and alcohol-related cue exposure (A1, M, and A2) in both the in vivo cue session (p < 0.002) and the videotape session (p < 0.02). Post hoc comparisons among the groups to alcohol-related cues established that, in both sessions (p(in vivo) = 0.04; p(videotape) = 0.04), the ADG demonstrated the greatest urge to drink. CONCLUSIONS: Alcohol cue reactivity can be reliably induced and assessed in alcohol-dependent participants via personalized videotapes. History of alcohol consumption is positively correlated with the degree of cue reactivity. This study advances our ability to assess alcohol cue reactivity in the absence of alcohol.

Adult↗
PubMed2002

Increase of rat alcohol drinking behavior depends on the age of drinking onset.

BACKGROUND: Although alcohol drinking onset in younger people is associated with an increased risk of alcohol-related injuries, other factors, such as habituation and susceptibility to alcohol, in the process of aging have not been adequately examined in animal models. In the present study, we determined whether age of drinking onset affected alcohol drinking behavior and led to alcohol tolerance in experimental animals, and extrapolated some of the findings to human alcohol drinking patterns. METHODS: In the first experiment, 18 rats that were naive to alcohol were tested at the age of 1, 4, and 10 months with 4 hr of access to 10% (v/v) alcohol. After the time access tests, these animals (1, 4, and 10 months of age) were housed individually and given free access to 10% alcohol solution and tap water. At 3 and 6 months later, all rats that had experienced alcohol drinking were studied for the voluntary consumption of the alcohol solution, alcohol preference, under the two-bottle method in a second experiment. RESULTS: In the 4-hr alcohol-access test, alcohol intake (g/kg/hr) was significantly increased at 0.5 and 1 hr in 1- and 4-month-old naive rats compared with 10-month-old naive rats. The daily alcohol intake (g/kg/day) of rats with drinking onset at 1 month of age was significantly increased at 3 and 6 months after the voluntary alcohol consumption. The daily alcohol intake in the rats with drinking onset at 4 months of age was significantly increased at 6 months only. However, the daily alcohol intake did not change in the rats with drinking onset at 10 months of age through the alcohol preference test. CONCLUSIONS: Alcohol drinking behavior in experimental animals depends on the age of alcohol drinking onset.

Age Factors↗
PubMed1989

Anatomical mapping of tetrahydropapaveroline-reactive sites in brain mediating suppression of alcohol drinking in the rat.

In a previous study, anatomically circumscribed sites were identified within limbic-midbrain and limbic-forebrain structures of the rat in which injections of tetrahydropapaveroline (THP) evoked the drinking of alcohol even at aversive concentrations. The purpose of the second part of this study was to identify specific sites in the same limbic structures which also were reactive to THP but which mediated the suppression of alcohol consumption. Cannulae for repeated microinjection of THP were implanted stereotaxically in male Sprague-Dawley rats at sites extending from the ventral tegmental-substantia nigra complex rostrally to the region of the olfactory tubercle. Postoperatively, the rats were tested for their self-selection of water versus alcohol offered in solutions increased over 10 consecutive days in 10 concentrations from 3 to 30%. THP was dissolved in a CSF vehicle containing Na2S2O5 or ascorbate and microinjected in a dose of 25, 50 or 250 ng contained in a volume of 1.5-2.0 microliters. Following a sequence of 5 microinjections of THP, given over 3 days, the same 10-day alcohol drinking test was repeated. Ordinarily, sites at three depths 1.0-1.5 mm beneath the tip of the guide tube were tested for their reactivity to the amine-aldehyde adduct. When injected at 21 sites within coronal planes 1.0-10.5, THP attenuated the intake of alcohol significantly. Structures sensitive to the inhibitory action of the aldehyde adduct included the substantia nigra, reticular formation, medial lemniscus, preoptic area, nucleus accumbens, olfactory tubercle, cingulate gyrus and rostral hippocampus. Within 65 loci contained within the same AP planes, little or no effect of alcohol intake was exerted by THP independent of the dose microinjected. Nonreactive loci were identified within fiber pathways including the corpus callosum and optic tract, motor systems of the caudate nucleus, and both sensory and motor relay nuclei of the thalamus. An analysis of the critical part played by the dose of THP revealed that 81% of reactive sites given the 25 ng dose mediated enhanced drinking of alcohol, as demonstrated in the first study. Conversely, the 50 and 250 ng doses injected at THP-sensitive loci reduced alcohol consumption three to seven times more often than they augmented drinking. Anatomical sites mediating an attenuation of alcohol consumption in response to the higher doses of THP overlapped with both enkephalinergic and dopaminergic systems which project from the ventral tegmentum and substantia nigra to the rostral limbic-forebrain.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcohol Drinking↗
PubMed1998

Development of alcohol drinking behavior in rat lines selectively bred for divergent alcohol preference.

A characteristic of heritable alcoholism is an early onset of alcohol abuse, which may begin at or before the age of adolescence. The objective of the present study was to determine the ontogeny of alcohol drinking behavior before and during puberty in the selectively bred alcohol-preferring (P), alcohol-nonpreferring (NP), high alcohol drinking (HAD), and low alcohol drinking (LAD) lines of rats. In addition, the effects of postweaning housing conditions (single- or pair-housed) and initiation procedure (4 days forced ethanol or free-choice) were evaluated in male and female P rats. Results indicate that high alcohol drinking in P and HAD (replicate line 2) rats, as well as low alcohol drinking behavior in NP and LAD (replicate line 2) rats, is present as early as 3 to 4 weeks of age. Ethanol intakes in juvenile P and HAD rats reached levels of approximately 4 to 5 g/kg/day by 38 to 41 days of age and were comparable with levels observed in adults. Neither housing conditions nor ethanol initiation procedure significantly altered the acquisition or magnitude of alcohol intake levels in juvenile male and female P rats. These results suggest that the neural substrates underlying divergent ethanol drinking behavior in P/NP and HAD/LAD lines of rats are present early in life.

Age Factors↗
PubMed1999

[Drinking alcohol among junior high school students: reflecting drinking culture].

Using a data obtained from a junior high school students survey on drug use, perception of alcohol drinking for junior high school students and role of adults in drinking were examined. 78% of the junior high school students had ever drunk alcohol at least once. The results revealed that experience of drinking alcohol accompanied by family did not have a close relationship with regularity of daily life routine, school lives and family lives for the students. It was, however, strongly suggested that experience of drinking alcohol only with peers had a close relationship with undesirable daily life routine, school lives and family lives for the students. Furthermore, lifetime prevalence of cigarette smoking and that of solvent inhalation for the male students with experience of drinking only with friends were 11 to 13 times and 5 to 8 times higher, respectively, than the male students without experience of drinking only with friends. These were 22 times and 3 to 5 times, respectively, for female students. As for observance of the law which prohibits drinking alcohol for those under 20 years old, over a half of the students consider that alcohol drinking for minors was acceptable depending on the time and circumstances. This was greatly different from the observance of the laws against cigarette smoking and solvent inhalation. The author considers that this may reflect adult alcohol drinking culture in Japan.

Adolescent↗