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PubMed2001

The role of GABAergic neuroactive steroids in ethanol action, tolerance and dependence.

This article reviews data on ethanol and neurosteroid interactions in the CNS. We discuss how GABAergic neurosteroids, including 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC, produced in response to systemic ethanol administration contribute to several of the effects of ethanol associated with modulation of GABA(A) receptors in rodents. There is an essential correlation between the time course of ethanol-induced 3alpha,5alpha-TH PROG production in the brain and specific behavioral and neural effects of ethanol. Furthermore, the anticonvulsant and inhibitory effects of ethanol on spontaneous neural activity were completely prevented by a key inhibitor of steroid biosynthesis. 3alpha,5alpha-TH PROG influences cognitive processing, spatial learning and memory and alters drinking behaviors in rats. Furthermore, ethanol induction of 3alpha,5alpha-TH PROG is diminished in tolerant and dependent animals. These effects are associated with increases in the sensitivity of GABA(A) receptors to neurosteroids and suggest an important role in ethanol withdrawal. Together, we suggest that 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC contribute to ethanol action and this interaction may represent a new mechanism of ethanol action. The identification of neurosteroid intermediaries involved in ethanol action may lead to important advances in the field and the development of novel therapeutics for alcoholism.

Alcoholism↗
PubMed2002

Carbohydrate-deficient transferrin levels reflect heavy drinking in alcohol-dependent women seeking treatment.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) is a biochemical marker that has been shown to be sensitive in detecting heavy drinking in men, but studies examining CDT in women have been inconsistent because of small sample sizes and failure to consider hormonal status. In healthy female subjects, CDT levels are significantly higher in premenopausal women with higher estradiol (E2) levels (>30 pg/ml) and those taking exogenous estrogens (oral contraceptives, hormone replacement therapy) compared with men and postmenopausal women. This study examined the relationship between drinking behavior and CDT levels in a large sample of alcohol-dependent women and contrasted findings in a comparison group of alcohol-dependent men. The study also examined the extent that E2 levels mediated the relationship between CDT levels and heavy drinking in the alcohol-dependent women. METHODS: This study examined the association between CDT level at treatment entry and alcohol consumption the month before initiating treatment in 96 women with a DSM-III-R diagnosis of alcohol dependence, as compared with similar data in 123 male alcoholics. To explore the relationship between E2 and CDT, E2 was measured in women at the time of CDT sampling. Linear regression was used to examine whether patterns of alcohol consumption in the 28 days before the CDT blood sampling predicted the CDT level in women and men presenting for treatment for alcohol dependence. RESULTS: CDT levels were higher in women than men and were related to quantitative alcohol consumption (total standard drinks, percentage of days drinking, percentage of days of heavy drinking) in the month before initiating treatment, irrespective of E2 levels in women. CONCLUSIONS: These results suggest that in a larger sample of female alcoholics, the amount of alcohol consumed predicted CDT, similar to what has been reported in male alcoholics. The E2 status did not seem to mediate these results.

Adult↗
PubMed2004

Low-dose stimulatory effects of ethanol during adolescence in rat lines selectively bred for high alcohol intake.

BACKGROUND: The low-dose stimulatory effect of ethanol (EtOH) in rats has been hypothesized to reflect its hedonic effects and to be associated with a genetic predisposition toward high alcohol preference. To test the hypothesis that phenotypes associated with high alcohol preference in adulthood are also present in adolescent rats at the time of onset of alcohol drinking, the current study examined the effects of EtOH on locomotor activity (LMA) during adolescence in lines of rats selectively bred for divergent alcohol intakes. METHODS: Subjects were adolescent (31-40 days of age) rats from the alcohol-preferring (P) and -nonpreferring (NP) lines and from the high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) replicate lines. On day 1, all subjects (n = 8-10/line/gender/dose) received intraperitoneal saline injections and were placed in the activity monitor for 30 min. On day 2, subjects received intraperitoneal saline or 0.25, 0.50, 0.75, 1.0, or 1.5 g EtOH/kg. RESULTS: The LMA of male and female P rats was increased with low doses (0.25-0.75 g/kg) and decreased at the highest dose (1.5 g/kg) of EtOH. Similar effects were observed with low doses of EtOH on the LMA of HAD-1 and HAD-2 rats. None of the EtOH doses stimulated LMA in the NP, LAD-1, or LAD-2 rats, although all of the low-alcohol-intake lines of rats showed decreased LMA at the highest dose of EtOH. Only the P rats among the high-alcohol-consuming lines of rats showed decreased LMA at the highest dose of EtOH. CONCLUSION: Selective breeding for high alcohol consumption seems to be associated with increased sensitivity to the low-dose stimulating effects of EtOH and reduced sensitivity to the high-dose motor-impairing effects of ethanol. The expression of these phenotypes emerges during adolescence by the age of onset of alcohol-drinking behavior.

Age Factors↗
PubMed1984

Legislation raising the legal drinking age in Massachusetts from 18 to 20: effect on 16 and 17 year-olds.

The 1979 Massachusetts law raising the legal drinking age from 18 to 20 is examined--the effects on the drinking, drinking and driving, and nonfatal and fatal crash involvement of 16-17 yr-olds, teenagers immediately younger than those targeted by the law. Data from Massachusetts are compared with those from New York State, where the drinking age remained at 18. A total of 3 yr of survey data from the two states and 6 yr of data from the Department of Transportation's Fatal Accident Reporting System provide for pre- and postlaw comparisons. The findings suggest that raising the drinking age had minimal effects on the drinking behavior of Massachusetts teenagers. Although there was a significant reduction in nonfatal crashes in Massachusetts compared with New York, no decline in single-vehicle nighttime fatal crashes or in overall fatal crashes was observed. It is suggested that changes in the drinking age may offer some reduction in teenage driving after drinking and traffic crash involvement, but that teenage drinking and driving after drinking remain serious problems even in states that raise their drinking ages.

Accidents, Traffic↗
PubMed1984

[Effect of metoprolol on water drinking activity in Wistar Kyoto rats].

The study was undertaken to elucidate the effect of beta 1 adrenoceptor blocking agent, metoprolol, on water drinking activity in Wistar Kyoto rats (WKY). Both 7 day (10mg/kg/day) oral administration of metoprolol and propranolol did not produce any changes in the systolic blood pressure of WKY. However, metoprolol produced a significant decrease in heart rate in WKY. Neither the propranolol treated rats nor the control (non-drug group) rats showed any significant changes in heart rate. Heart rates were significantly changed in the metoprolol group as compared with the other two groups. This finding reconfirms that metoprolol has beta 1 selectivity. Drinking activity, an indicator of central nervous function, did not change after metoprolol administration. Power spectral analysis of water drinking activity did not reveal any changes in rhythm in respect to periodicity in the metoprolol group. Although water drinking activity is synchronized with urinary catecholamine and aldosterone excretion rates, urinary catecholamine and aldosterone excretion rates did not change after metoprolol administration. These findings suggest that it is the beta 1 adrenergic blocking action of a bradycardia-producing dose of metoprolol that prevented any change in water drinking behavior in WKY.

Aldosterone↗
PubMed2001

Sex and strain differences in ethanol drinking: effects of gonadectomy.

BACKGROUND: Alcohol drinking behavior in rats is known to be sexually dimorphic and strain-dependent. METHODS: To test whether the gonadal steroid milieu exerts activational effects on ethanol intake and can modulate individual sensitivity toward alcohol use and misuse, we examined the effects of gonadectomy on oral self-administration (OSA) of ethanol in male and female rats from different strains. After castration, animals were given continuous free choice between water and ethanol solutions. The ethanol concentration was progressively increased from 2% to 10% and maintained at 6% (the preferred concentration) for 24 days. Ethanol solutions were then withdrawn for 9 days. During the second phase of free-choice drinking, the ethanol concentration was gradually increased every 4 days by the following amounts, in order as listed: 6%, 12%, and 24%. RESULTS: Our results confirm both gender and strain differences in ethanol drinking: females exhibited higher ethanol intake than males, and the WKHA strain drank more than the WKY and SHR strains. However, except for a small decrease in ethanol drinking during the acquisition of ethanol OSA in males after castration, no clear-cut difference was found between gonadectomized and sham-operated animals during the maintenance of ethanol OSA behavior. CONCLUSIONS: These data suggest that gender and strain differences observed are insensitive to gonadal steroids during adulthood, and that different sensitivities to the effect of gonadal steroids do not explain the sex x strain interaction observed in ethanol drinking.

Alcohol Drinking↗
PubMed2000

Scanning of five chromosomes for alcohol consumption loci.

In our present genetic study to map Quantitative Trait Loci (QTLs) for alcohol-related behaviors, we used 44 B6.C and 36 B6.I inbred congenic Recombinant QTL Introgression (RQI) mouse strains of the b5i7 series carrying genes of BALB/cJ (C) or CXBI (I) origin on C57BL/6ByJ (B6) genetic background. Ethyl alcohol consumption (EAC) was measured in adult males, and chromosomes 1, 2, 3, 9, and 15 were scanned with polymorphic microsatellite markers. In the B6.C set of strains, multiple regression analysis yielded a model with three microsatellite markers, which explained 32% of the genetic variance (p=0.0006). The two markers with the highest significance levels in the model, D1Mit167 and D2Mit74, have been mapped to chromosome regions close to the gene opioid receptor kappa 1 (chr. 1) and opioid receptor kappa 3 (chr. 2), respectively. The results of this gene-mapping study suggest that genetic polymorphisms in kappa opioid receptors may contribute to genetic predisposition to voluntary alcohol-drinking behavior.

Alcohol Drinking↗
PubMedDate not supplied

Circadian drinking rhythms and blood alcohol levels in two rat lines developed for their alcohol consumption.

The circadian drinking behavior of the AA (Alko Alcohol) and ANA (Alko Non-Alcohol) rat lines developed for high and low voluntary alcohol consumption was studied by using a microcomputer lick-counting system. The blood alcohol concentrations of AA rats were measured during the drinking peaks. The results showed that AA rats voluntarily drink intoxicating amounts of alcohol. The highest blood alcohol levels were about 25 mmol/l. Differences in circadian drinking rhythms between AA and ANA lines were also found. AA rats had a trimodal drinking pattern for alcohol intake during the dark period but ANA rats drank alcohol rather evenly throughout the period.

Alcohol Drinking↗
PubMed2003

Predictors of change in binge drinking over a 3-month period.

Self-efficacy and positive and negative alcohol expectancies have been associated with drinking reduction for some groups, but the relationship of these constructs with changes in high-risk binge drinking behavior among young adults over time is poorly understood. Seventy-six young adults between the ages of 18-32 were recruited to examine this question. Lower self-efficacy and greater positive alcohol expectancies predicted greater numbers of follow-up binge drinking episodes, and greater positive alcohol expectancies predicted greater follow-up alcohol consumption. Young adults with lower self-efficacy, and greater numbers of positive alcohol expectancies may be at risk for experiencing a worsening binge pattern over time.

Adolescent↗
PubMed2002

D(2) dopamine receptor (DRD2) polymorphism is associated with severity of alcohol dependence.

The A(1) allele of the D(2) dopamine receptor (DRD2) gene has been associated with alcohol dependence. However, the expression of this allele risk on the severity of drinking behavior in patients with alcohol dependence has not been systematically explored. The present study examines the association between DRD2 A(1)(+) (A(1)/A(1) and A(1)/A(2) genotypes) and A(1)- (A(2)/A(2) genotype) allele status and key drinking parameters in alcohol-dependent patients. A sample of Caucasian adults was recruited from an alcohol detoxification unit. A clinical interview and the Alcohol Dependence Scale (ADS) questionnaire provided data on consumption, dependence, chronology of drinking and prior detoxification. A(1)(+) allele compared to A(1)- allele patients consumed higher quantities of alcohol, commenced problem drinking at an earlier age, experienced a shorter latency between first introduction to alcohol to the onset of problem drinking and had higher ADS scores. Moreover, A(1)(+) allele patients had more detoxification attempts than their A(1)- allele counterparts. In sum, alcohol-dependent patients with the DRD2 A(1) allele compared to patients without this allele are characterized by greater severity of their disorder across a range of problem drinking indices. The implications of these findings are discussed.

Adult↗
PubMed1984

Measuring the success of occupational alcoholism programs.

The research on the success of occupational alcoholism programs (OAPs) was reviewed. One measure of the success of OAPs has been a change in drinking behavior. This may seem like the most relevant measure but there are questions about its reliability because researchers usually depend on subjects' self-reports and do not define their criteria for successful outcome well. In addition, attempts by employers to dictate the drinking habits of their employees may be difficult to justify. Varying rates of success on this measure have been reported. Subjects have generally been able to control drinking in the long term, but it is suggested that their control erodes over time. A second measure of the success of OAPs has been work performance, as revealed by absenteeism, disciplinary actions, accidents, sick and injured days taken, turnover rate and job efficiency. Studies of this measure have been hindered by employers' poor record keeping and by the difficulty of developing standard measures of outcome success. In general, studies with weaker research designs have shown more improvement on this measure. A third measure has been the cost efficiency of OAPs, as revealed by direct savings for employers resulting from OAPs such as decreases in absenteeism and indirect savings such as increased accuracy of work. This measure seems to be the one most relevant to employers' profit motives. Studies of cost efficiency have had ambiguous findings. A fourth measure has been the penetration rate--the extent to which an OAP reaches its target population. This measure has never been studied successfully. A problem with all the studies reviewed has been their poor design (a lack of control groups, follow-up periods that were too brief and problems with selection of subjects), which raises serious questions about their validity. The obstacles to measuring outcome success were also discussed--poor documentation by employers, lack of access to subjects and reluctance on the part of employers and treatment staff to allow studies.

Absenteeism↗
PubMed1999

Changes in alcohol consumption patterns following the introduction of credit cards in Ontario liquor stores.

OBJECTIVE: In 1994, regulatory changes were introduced in Ontario, Canada, permitting the purchase of alcoholic beverages with credit cards at government-operated liquor stores. Two objectives of this study were: (1) to compare the characteristics of credit card shoppers with non credit card shoppers at liquor stores, and (2) to assess whether changes occurred in alcohol consumption patterns among shoppers following the introduction of credit cards. METHOD: Random digit dialing was used to interview 2,039 telephone participants prior to the introduction of credit cards (Time 1); 1,401 of these subjects were contacted 1 year later (Time 2). Independent sample t tests were used to compare credit card shoppers with shoppers not using credit cards, and paired t tests were performed to assess whether drinking behaviors changed from Time 1 to Time 2. RESULTS: The credit card shoppers were more likely than the non credit card shoppers to be highly educated (p < .001) and to have high incomes (p < .05). Credit card shoppers drank an average of 6.3 drinks over the previous week compared with 4.0 drinks among non credit card shoppers (p < .01). Although the overall amount of alcohol consumed among credit card shoppers dropped from 6.7 drinks at Time 1 to 6.3 at Time 2 (NS), credit card shoppers reported drinking significantly more often after credit cards were introduced (p < .05). CONCLUSIONS: The results suggest that credit cards may not present public health problems since significant increases in alcohol consumption among credit card shoppers were not found.

Adolescent↗
PubMed1990

Ingestive behaviors of the rat deficient in vasopressin synthesis (Brattleboro strain). Effect of chronic treatment by dDAVP.

Spontaneous manipulator and locomotor activities, food and fluid intake have been recorded from rats suffering from a genetic lack of central vasopressin (VP) synthesis (Brattleboro strain, DI), their heterozygous litter mates (HZ) or Long Evans (LE) rats. The daily patterns of activities did not differ, except for their drinking behavior. This was mainly associated with food intake during the dark period with LE rats but was distributed equally during light and dark periods with DI rats. HZ rats showed a behavioral heterogeneity, some of them following the daily pattern of LE rats, and others, that of DI rats. The daily feeding pattern was identical in the three genotypes but the selection between two isocaloric contrasted diets was different. When they were fed ad lib, HZ and DI rats consumed less carbohydrate than LE rats, the protein intake being unchanged. On the contrary, when the DI rats were only fed during the dark period, they ate more carbohydrate than LE rats. The peripheral infusion of a V2 AVP agonist (dDAVP) restored a normal hydric balance in DI rats but failed to modify the diet selection. These data show that in the rats, the lack of central VP synthesis disturbs both the selection of diets and the efficiency of the satiety signals. These disturbances were unchanged by the peripheral VP treatment which suggested the direct involvement of the central release of the neuropeptide.

Animals↗
PubMedDate not supplied

Health assessment for partners of pregnant women: a pilot study of four survey methods.

BACKGROUND: Health assessment for partners of pregnant women has not been routinely offered. Work in the area of smoking cessation suggests that a partner's health habits have a strong influence on the health habits of a pregnant woman. Smoking, alcohol abuse, depression, battering, and household firearms cab adversely affect the health of the expectant mother and the infant. METHODS: Four methods of partner assessment were pilot tested: office visit with a family physician, office visit with a registered nurse, telephone survey conducted by the registered nurse, and mailed questionnaire. Written feedback and referrals were provided to all study participants, and verbal feedback and referrals were provided to those who completed in-person or telephone interviews. A chart review was conducted to determine participation bias. RESULTS: Thirty-five pregnant women and 25 partners participated in the study. Self-administered questionnaires and telephone interviews were preferred by study participants. The study group was healthier than the general population. Five partners reported troublesome drinking behavior, and 1 reported smoking two packs of cigarettes per day. CONCLUSIONS: health assessment of partners of pregnant women seems promising for uncovering health problems that would be likely to have an adverse impact on the health of the family. Further development of assessment and intervention strategies is needed.

Adult↗
PubMed1994

[A comparison between wheel-running and ambulatory activities in young, adult and old rats based on long-term observation].

It has been considered that spontaneous motor activity (SMA) represented by wheel-running activity (WRA) or ambulatory activity (AA) is one of the most basic indicators in the behavioral-pharmacological test in small rodents. Since various differences are noticeable between WRA and AA in their characteristics or drug responses, both activities may be not considered as the same category of SMA. The main purpose of this study was to elucidate the background difference between WRA and AA in three different aged groups, based on their long-term observation. AA data obtained by Gundai type Ambulo-drinkometer were applied for comparison with WRA data obtained by Wheel-drinkometer. WRA, AA and drinking behavior all showed clear diurnal rhythms characterized by nocturnal animals under light-dark condition (LD = 12:12 h). WRA and AA, in particular the former, tended to decrease according to the aging. More than 30 days habituation was required in order to obtain stable daily WRA level in adult rats. AA of young rats was higher than the other aged rats. The present results suggest that indicators, conditions, measurement apparatus, age etc have to be considered in behavioral-pharmacological observations using WRA or AA.

Aging↗
PubMed2005

Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats.

The purpose of the present study was to investigate whether Lewis (LEW) and spontaneously hypertensive rats (SHR), characterized in numerous behavioral tests as strains with high-anxiety and low-anxiety, respectively, could differ in their sensitivity to the effects of ethanol in the elevated plus maze (EPM) and the open field (OF), two classical models of anxiety/emotionality, as well as in the acquisition of ethanol drinking behavior. It was also of interest to examine the relationship between sweet and bitter fluids preference and ethanol intake. SHR and LEW rats were given saline or ethanol injections (0.6 or 1.2 g/kg, ip.) and tested in the EPM and OF. Subsequently the same animals were given continuous free choice between water and ethanol solution (2-8%). Additional groups of animals were exposed to a free-choice regimen between saccharin (0.002-0.09%) or quinine (0.0001-0.0015%) and water. The low dose of ethanol (0.6 g/kg) induced anxiolytic-like effects and intensive locomotor activation mainly in SHR rats tested in the OF arena. Overall, LEW counterparts were unaffected in OF test. In oral self-administration paradigm, SHR rats consumed significantly more ethanol than LEW rats. Concerning other solutions, SHR rats consumed large amounts of saccharin compared with LEW rats. These data indicate that the SHR preference for ethanol intake may be positively related to their differential sensitivity to the anxiolytic/stimulant effects of ethanol and to the sensitivity of this strain for saccharin reinforcement. In addition, these findings provide evidence that the SHR strain may represent a useful genetic and pharmacological tool to investigate ethanol drinking traits.

Alcohol Drinking↗
PubMed1988

Involvement of kappa type opioids on ethanol drinking.

The effects of the administration of the kappa agonist dynorphin1-17 and/or the kappa antagonist MR-2266-BS on ethanol preference was investigated using a paradigm by which rats develop alcohol preference. Administration of dynorphin shortly before or after the conditioning session (forced ethanol exposure) failed to affect later ethanol preference. However, dynorphin treatment prior to the first choice session reduced ethanol preference during the three consecutive testing days. This effect was reversed by the simultaneous administration of the kappa antagonist MR-2266-BS. The results of the present study provide further support for evidence of the involvement of dynorphinergic systems on drinking behavior and suggest that kappa-type opioid mechanisms may be involved in the consumption and development of preference to ethanol in rats.

Alcohol Drinking↗