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Adjustment to intermittent access in rats drinking saccharin: I. Pauses in drinking.

Hungry rats drink saccharin solutions avidly. When access to the cylinder is restricted, so that it is available during alternate 30-sec periods rather than continuously, rats adjust to this constraint so that total amount of lapping, over each period of a few minutes each, is defended. We show that the rats achieve this defense, in part, by pausing less often and for briefer periods between bursts. Log-survivorship analysis of the pauses in drinking suggests (a) that they are generated by two processes with different time constants, (b) that early in the session, both processes are suppressed when access is restricted; and (c) that later in the session, pauses reflecting the shorter-term process begin to appear, even if access is restricted. Therefore, adjustment to constraints on access is achieved in part by suppression or inhibition of two processes that generate pauses, and the suppression is relaxed earlier for the one with shorter time constant.

Animals↗

To drink or not to drink: tests of anxiety and immobility in alcohol-preferring and alcohol-nonpreferring rat strains.

Previous reports have provided mixed results about emotional states in rats that voluntarily drink substantial amounts of alcohol. The purpose of the present study was to compare several strains of alcohol-preferring rats (P, AA, FH) with several strains of alcohol-nonpreferring rats (NP, ANA, FRL), and the Maudsley strains on tests reflecting anxiety and immobility. At about 70 days of age the rats were placed in the elevated plus maze for a 5-min test; a forced swim test of 10 min was given 4 days later and this test was followed 4 days later by a modified forced swim test (the capsule), in which there were four false escape alleys. The FRL rats spent more time in the open arms of the elevated plus maze than any other strain, but there was no consistent relationship between elevated plus maze scores and alcohol intake. The alcohol-preferring P rats were the most active in the standard forced swim test and the alcohol-nonpreferring Maudsley Reactive rats were the least active, but there was no consistent relationship between immobility and alcohol intake overall. All rats were much more active in the capsule and there were no significant strain differences. However, the alcohol-preferring P and FH rats attempted to escape more than the other strains, resulting in an overall significant correlation between escape attempts and alcohol intake. These findings do not provide any support for the hypothesis that alcohol-preferring rats are drinking alcohol to reduce high anxiety states.

Alcohol Drinking↗

To drink or not to drink? Assessing conflicting desires in dependent drinkers in treatment.

Reactivity to Alcohol and Neutral Cues was compared in male, inpatient problem drinkers (N = 30). Subjects reported an overall desire not to drink alcohol which decreased in the presence of the Alcohol Cue. There were no cue-specific changes in heart rate, blood pressure and arousal level and a non-significant trend for increased stress in the Alcohol Cue condition. Subgroups of subjects reporting positive and negative desire for alcohol were identified. Subjects who reported negative desire for alcohol in the Alcohol Cue condition also reported greater self-efficacy to resist drinking in the future. These findings have implications for understanding the nature of self-reported desire for alcohol and its potential role in the treatment of alcohol dependence.

Adult↗

Acetaldehyde-reinforcing effects: differences in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

It has been suggested that acetaldehyde has a biphasic effect on voluntary alcohol consumption. At low brain concentration, it might exert reinforcing effects, whereas high acetaldehyde levels would be predominantly aversive. The objective of the current study was to compare the effect of an intraperitoneal dose of acetaldehyde (50 mg/kg) in high-alcohol-drinking (UChB) and low-alcohol-drinking (UChA) rat lines, which differ in the activity of the brain mitochondrial class 2 aldehyde dehydrogenase (ALDH2) as a consequence of differences in their ALDH2 genotypes. A classical place-conditioning procedure was used to determine the reinforcing or aversive (or both) effects of acetaldehyde in ethanol-naive UChB and UChA rats. Environmental cues were paired with an intraperitoneal 50-mg/kg injection of acetaldehyde. On 10 consecutive days, each rat received one place conditioning per day; the acetaldehyde-pairing was alternated with saline-pairing. Results showed that conditioning with the 50-mg/kg dose of acetaldehyde induced place preference in UChB rats and place aversion in UChA rats. In a second experiment, UChB and UChA rats, pretested for ethanol preference, were injected with one 50-mg/kg dose of acetaldehyde or saline and tested for their voluntary ethanol consumption during 4 weeks. Results showed that the acetaldehyde dose induced a persistent and long-lasting enhancement of ethanol intake in UChB rats, but not in UChA rats. These results, together with the finding that after administration of a 50-mg/kg dose of acetaldehyde cerebral venous blood acetaldehyde levels in UChA rats were consistently higher than levels in UChB rats, support the suggestion that differential acetaldehyde levels, differential brain ALDH2 activity, or both were responsible for the different effects of acetaldehyde in the two rat lines.

Acetaldehyde↗

Differences in sensitivity to the aversive effects of ethanol in low-alcohol drinking (UChA) and high-alcohol drinking (UChB) rats.

A conditioned taste aversion paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to differences in voluntary ethanol consumption in rats of the low-alcohol drinking (UChA) and the high-alcohol drinking (UChB) strains. "Alcohol-naive" UChA and UChB rats were injected intraperitoneally with ethanol (0.5, 1.0, 1.5, or 2.0 g/kg) or saline, paired with consumption of a banana-flavored solution during five conditioning trials. Repeated pairings of banana-flavored solution and ethanol at a dose of 1.5 g/kg produced aversion to the banana-flavored solution in UChA rats, but not in UChB rats, at comparable blood ethanol levels. In addition, the highest dose of ethanol tested (2.0 g/kg) produced stronger aversion to the banana-flavored solution in UChA rats, compared with findings in UChB rats. From these results it is suggested that rats of the UChA strain find the postingestional effects of high-dose ethanol more aversive than do UChB rats. Differences in voluntary ethanol consumption seem to be associated with differences in sensitivity to the aversive effects of ethanol.

Alcohol Drinking↗

Aversion to acetaldehyde: differences in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

We have previously found the existence of a relation between activity of the brain mitochondrial aldehyde dehydrogenase (ALDH2) and consumption of ethanol in rats of the low-alcohol-drinking (UChA) and the high-alcohol-drinking (UChB) strains. The aim of the present study was to determine whether UChA and UChB rats also differed in sensitivity to the aversive effects of acetaldehyde (AcH). Aversion to AcH was studied by using a conditioned taste aversion (CTA) paradigm. Ethanol naive UChA and UChB rats were administered AcH intraperitoneally (50, 100, or 150 mg/kg) or saline and exposed to a banana-flavored solution during five conditioning trials. A strong dose-dependent CTA to AcH was found in UChA rats, whereas UChB rats did not show a CTA to any dose of AcH. At equal doses of AcH, cerebral venous blood AcH levels in UChA rats were consistently higher than in UChB rats, a finding that may reflect the previously observed differences in the activity of ALDH2 between these strains. However, this observation is unlikely to explain fully the differences observed because aversion to AcH was developed in the UChA strain at blood levels of AcH that did not produce any aversion in the UChB strain. These results support the suggestion that, for the first time, differences in central or systemic effects of AcH per se may play a major role in determining the aversion to AcH in drinker and nondrinker animals.

Acetaldehyde↗

Identification of quantitative trait loci influencing alcohol consumption in the high alcohol drinking and low alcohol drinking rat lines.

Selective breeding has been employed to develop high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rat lines from the heterogeneous N/Nih rat. Within-family selection and a rotational breeding design were used to discourage inbreeding (Li et al, 1993). To identify quantitative trait loci (QTLs) contributing to alcohol consumption, reciprocal HAD and LAD matings in conjunction with F1 intercrosses were used to create 459 F2 progeny. Using selective genotyping of 151 F2 progeny with extreme alcohol consumption scores and a novel least squares method developed by Haley et al (1994), five chromosomal regions (1, 5, 10, 12, and 16) were identified with lod scores greater than 2.0. Genotyping of the entire sample of 459 F2 progeny produced maximum lod scores of 3.5 on chromosome 5, 2.4 on chromosome 10, 4.7 on chromosome 12 and 2.9 on chromosome 16. The evidence of linkage to chromosome 1 diminished substantially to a maximum lod score of 0.5 when all F2 progeny were genotyped. This study is the first genome-wide study for QTLs underlying alcohol consumption that has employed noninbred lines. Further localization of these QTLs will likely provide insight and candidate genes for the study of human alcoholism.

Alcohol Drinking↗

The development of alcohol consumption and problem drinking in Rotterdam 1980-1994: more problem drinking amongst the young and the middle aged.

In 1980/1981 and in 1994, two surveys on problem drinking were conducted in the city of Rotterdam. This article presents data on changes in alcohol consumption and alcohol-related problems between 1981 and 1994. Special attention has been paid to possible shifts in groups at risk and to shifts in the kind of problems experienced. It was found that, in 1994, compared to 1981, problem drinking had become more prevalent amongst the young and the middle aged.

Adolescent↗

Psychosocial characteristics and follow-up of drinking and non-drinking drivers in motor vehicle crashes.

Eight hundred fifty-four consecutive motor vehicle crash (MVC) victims admitted from August 1, 1986, through August 31, 1989, were prospectively assessed including measurement of blood alcohol concentration (BAC). One hundred six in-hospital interviews were conducted on competent consenting drivers > or = 18 years old; 22.9% (n = 22) of those who were BAC tested (n = 96) were positive for alcohol on admission. The blood alcohol concentration positive [BAC(+)] and the BAC negative (-) drivers differed significantly on the following variables; driver education [BAC(-) > BAC(+): p < 0.01], license suspension < or = 2 years before admission [BAC(+) > BAC(-): p < 0.01], frequency of self-reported intoxication in month before crash [BAC(+) > BAC(-): p < 0.05], driving within 2 hours of drinking < or = 1 month before admission [BAC(+) > BAC(-): p = 0.01] and self-reported driving with BAC > 17 mmol/L < or = 1 month before admission [BAC(+) > BAC(-): p < 0.01]. Follow-up interviews (n = 106) were conducted 1 year after discharge; drivers originally testing BAC(+) were more likely to drive within 2 hours of drinking (p < 0.05), and were more likely to admit to driving with a BAC > 17 mmol/L (p < 0.01). Original BAC(+) drivers were also more likely to report a subsequent MVC in the year following discharge (not statistically significant). There is a need to develop an assessment system to identify high crash-risk drivers and establish rehabilitation programs to reduce crash recidivism.

Accidents, Traffic↗

Confirmation of alcohol preference quantitative trait loci in the replicate high alcohol drinking and low alcohol drinking rat lines.

OBJECTIVE: Selective breeding has been employed to develop replicate high-alcohol-drinking (HAD1 and HAD2) and low-alcohol-drinking (LAD1 and LAD2) rat lines from the heterogeneous N/Nih rat. Within-family selection and a rotational breeding design were used to discourage inbreeding (Li et al., 1993). A genome screen was previously performed using 459 HAD1xLAD1 F2 progeny to identify quantitative trait loci (QTLs) on rat chromosomes 5, 10, 12 and 16 that contribute to alcohol preference and consumption in these non-inbred rat models of alcoholism. METHODS: To confirm these QTLs in the replicate lines, 16 HAD2 and 16 LAD2 rats were genotyped for microsatellite markers within each of these QTL intervals. RESULTS: Review of the genotypic data support confirmation of the QTLs on chromosomes 5 and 10; several markers in the QTL region display different alleles in the HAD2 and LAD2 rats, suggesting linkage disequilibrium between the microsatellite markers and the QTL. Although the QTL on chromosome 12 had the highest LOD score in the HAD1 and LAD1 studies, little evidence supported confirmation of this QTL based on the genotyped markers. CONCLUSIONS: Further evaluation of each of these QTL regions is ongoing in a sample of HAD2xLAD2 F2 progeny currently being generated that will be used to assess the evidence of linkage in each of these QTL regions.

Alcohol Drinking↗

Neurophysiological profiles of replicate line 2 high-alcohol-drinking (HAD-2) and low-alcohol-drinking (LAD-2) rats.

RATIONALE: A select number of electrophysiological findings have been demonstrated to differentiate rat lines selectively bred for high and low ethanol preference. OBJECTIVE: In the present study, EEGs and event-related potentials (ERPs) of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats from replicate line 2 (HAD-2 and LAD-2) were assessed to determine if their neurophysiological profiles are similar to selected lines previously evaluated. METHODS: Rats obtained from Indiana University were implanted with cortical and amygdalar recording electrodes. Baseline EEG and ERPs were assessed in ethanol-naïve HAD-2 and LAD-2 rats. Animals subsequently were trained to self-administer ethanol by using a sucrose-substitution procedure. RESULTS: Compared with LAD-2 rats, HAD-2 rats displayed greater parietal cortical power in the 6 to 32 Hz frequency range of the EEG. Greater parietal cortical peak frequency in the 2 to 4 Hz range and decreased frontal, parietal, and amygdalar peak frequencies in the 16 to 32 Hz frequency range were also seen. Compared with LAD-2 rats, HAD-2 rats had decreased P2 latency of ERPs recorded in the parietal cortex. HAD-2 rats also had greater frontal, parietal, and amygdalar P2 amplitudes, greater frontal and parietal cortical P1 amplitudes, and greater parietal cortical P3 amplitudes compared with LAD-2 rats. As anticipated, HAD-2 rats consumed significantly greater levels of sucrose, sucrose-ethanol, and ethanol over the course of the sucrose-substitution procedure compared with LAD-2 rats. CONCLUSIONS: These data suggest that increased cortical power is associated with high ethanol preference in a number of selectively bred rat lines. However, unique electrophysiological characteristics may index alcohol preference in each line.

Alcohol Drinking↗

Drinks of the father: father's maximum number of drinks consumed predicts externalizing disorders, substance use, and substance use disorders in preadolescent and adolescent offspring.

BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses. METHODS: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures. RESULTS: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.

Adolescent↗

Differential responding for brain stimulation reward and sucrose in high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats.

BACKGROUND: This study examined the associations among selective breeding for alcohol preference, intake of sweet solutions, and responding for brain stimulation reward (BSR), a nonoral reinforcer, in alcohol-preferring high-alcohol-drinking (HAD)-1 and nonpreferring low-alcohol-drinking (LAD)-1 rats. METHODS: Adult male HAD-1 and LAD-1 rats were trained to lever press for medial forebrain bundle stimulation. Current intensity was varied in separate sessions to generate a rate/intensity function. To further examine BSR responding, the animals responded for stimulation at 100 Hz and at a fixed current intensity on an FR1 schedule. In subsequent sessions, the schedule was increased to FR6 and then to FR12. To examine responding for the sucrose solution, we trained a separate group of HAD-1/LAD-1 rats to bar press for sucrose on an FR1 schedule. Similar to the BSR experiment, in following sessions, the schedule was increased to an FR6 and then to an FR12 schedule. RESULTS: No significant differences were observed between the two rat lines across a range of current intensities. As the reinforcement schedule increased, HAD-1 rats exhibited a dramatic decrease in BSR responding, whereas the LAD-1 rats displayed a more protracted reduction. In contrast to BSR, marked elevations in responding were observed for sucrose as the schedule increased. However, in HAD-1 rats, response rates were similar on the FR6 and FR12 schedules, whereas LAD-1 rats showed a reduction in response rates from the FR6 to FR12 schedule. Furthermore, HAD-1 rats exhibited significantly more responses compared with LAD-1 rats across the three reinforcement schedules. An analysis of the response profile for the three reinforcement schedules suggested that few if any postreinforcement pauses were exhibited when the reinforcer was BSR compared with sucrose in both lines. CONCLUSION: Medial forebrain bundle BSR is a powerful reinforcer in both HAD-1 and LAD-1 lines. However, BSR responding was not associated with selective breeding for alcohol preference. In contrast, selective breeding for alcohol preference was associated with sucrose consumption, especially as the amount of work increased. The lack of correspondence between BSR and sweet taste rewards in HAD-1 and LAD-1 lines may suggest important differences yet an overlapping brain reward mechanism in the control of motivated behaviors in these selected lines.

Alcohol Drinking↗

Alcohol use disorder among adolescents: impact of paternal alcoholism on drinking behavior, drinking motivation, and consequences.

This study examined the impact of an Alcohol Use Disorder (AUD) in biological fathers on drinking history, context, motivation, and consequences in male and female adolescents dichotomized according to the presence or absence of an AUD. Main effects for paternal history of an AUD were not found on any variable. Significant interactions were observed between father-son diagnostic status with respect to age of first alcohol use (p < 0.001) and peer relationships (p < 0.001). No significant interactions were observed between father-daughter diagnostic status. As expected, adolescents with AUD differed from adolescents without AUD on numerous variables pertaining to drinking behavior, history, and consequences. These findings indicate that there is no strong or pervasive effect of paternal AUD on adolescent offspring's AUD characteristics.

Adolescent↗

Gastrointestinal function during exercise: comparison of water, sports drink, and sports drink with caffeine.

Caffeine is suspected to affect gastrointestinal function. We therefore investigated whether supplementation of a carbohydrate-electrolyte solution (CES) sports drink with 150 mg/l caffeine leads to alterations in gastrointestinal variables compared with a normal CES and water using a standardized rest-exercise-rest protocol. Ten well-trained subjects underwent a rest-cycling-rest protocol three times. Esophageal motility, gastroesophageal reflux, and intragastric pH were measured by use of a transnasal catheter. Orocecal transit time was measured using breath-H(2) measurements. A sugar absorption test was applied to determine intestinal permeability and glucose absorption. Gastric emptying was measured via the (13)C-acetate breath test. In the postexercise episode, midesophageal pressure was significantly lower in the CES + caffeine trial compared with the water trial (P = 0.017). There were no significant differences between the three drinks for gastric pH and reflux during the preexercise, the cycling, and the postexercise episode, respectively. Gastric emptying, orocecal transit time, and intestinal permeability showed no significant differences between the three trials. However, glucose absorption was significantly increased in the CES + caffeine trial compared with the CES trial (P = 0.017). No significant differences in gastroesophageal reflux, gastric pH, or gastrointestinal transit could be observed between the CES, the CES + caffeine, and the water trials. However, intestinal glucose uptake was increased in the CES + caffeine trial.

3-O-Methylglucose↗

[Alcohol drinking habits assessed by the AUDIT test. Reduced maximum levels doubled the number of women with dangerous alcohol drinking].

The Alcohol Use Disorders Identification Test (AUDIT) was completed by 997 persons randomly sampled from the general Swedish population (80 percent response rate). Eighteen percent of the men and 5 percent of the women had hazardous or harmful alcohol use according to the 8+ score criterion. Since women are more sensitive to alcohol than men, a cut-off score of 6+ was suggested for them. The female prevalence of hazardous or harmful alcohol use then increased to nearly 11 percent. Hazardous or harmful alcohol use decreased with increasing age in both genders. The "binge drinking" question explained half of the total AUDIT variance and is thus the best predictor of heavy drinking in the test. The internal and test-retest reliability of the AUDIT was satisfactory. Reference values for different ages and genders are presented.

Adolescent↗

Quantitative Autoradiography on [(35)S]TBPS Binding Sites of Gamma- Aminobutyric Acid(A) Receptors in Discrete Brain Regions of High- Alcohol-Drinking and Low-Alcohol- Drinking Rats Selectively Bred forHigh- and Low-Alcohol Preference.

It has been documented that ethanol can potentiate brain gamma-aminobutyric acid (GABA)ergic function, and there is a close link between the GABA(A) receptor complex and effects of ethanol, including reinforcement of alcohol which is a fundamental element of alcohol preference. However, it is unknown in what discrete brain regions GABA(A) receptors might be associated with alcohol preference. In the present study, [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) was used to localize GABA(A) receptors in high-alcohol-drinking (HAD) rats and low-alcohol-drinking (LAD) rats which were selectively bred for high and low alcohol preference, respectively. Initial qualitative observations indicated that [(35)S]TBPS binding sites were abundant in many brain areas including the cerebral cortex, hypothalamus and amygdala of HAD and LAD rats. Furthermore, the quantitative autoradiographic analysis revealed fewer [(35)S]TBPS binding sites of GABA(A) receptors in the amygdaloid complex, central medial thalamic nucleus, lateral hypothalamic nucleus and anterior hypothalamic nucleus of HAD rats than LAD rats. Collectively, this study has indicated that HAD rats selectively bred for high alcohol preference possess lower [(35)S]TBPS binding in the brain. Since lower TBPS binding has been proposed to reflect enhanced GABAergic function, as evidenced in rats with seizure or under alcohol withdrawal, the results from the present study suggest that HAD rats might have an enhanced GABAergic function. It is thus likely that enhanced GABAergic function in the brain might be related to high alcohol preference which is characteristic in HAD rats. In addition, the present result showing no difference of [(35)S]TBPS binding in the nucleus accumbens is also in agreement with a notion that [(35)S]TBPS binding may represent only a small spectrum of the GABA(A) receptor complex which is constituted of a sophisticated subunit combination whose functional compositions are still unknown. In conclusion, the present study supports the working hypothesis that GABA(A) receptors are involved in alcohol preference in HAD rats.

Journal Article↗