Cerebral Deficits in Social Drinkers and the Onus of Proof

Abstract: A number of correlational studies have claimed to show that moderate social drinking (less than 80 ml of ethanol per occasion) may give rise to chronic cerebral deficits. These claims are widely cited in the scientific literature and have been reiterated in the popular press. However, review of the evidence suggests that these claims suffer serious conceptual and methodological limitations. All of the data is open to more parsimonious interpretation. Abstinence studies have also failed to provide any evidence of a reversible toxic effect on behaviour. As a consequence, the onus rests with the proponents of the view that moderate alcohol consumption harms mentation to provide some unambiguous evidence.     

Influence of chlordiazepoxide on alcohol consumption in mice

In a free-choice situation, chlordiazepoxide (CDP; 12.5 or 25 mg/100 ml; groups B or C), when incorporated in ethanol solutions (2 to 20%, v/v), caused a significant decrease in ethanol preference index (P.I.). This was probably due to the combined CNS effects of both drugs rather than a taste effect, since the mice did not discriminate between aqueous CDP solutions and water. However, when the mice had prior exposure to ethanol and CDP was incorporated intermittently, no significant decreases in P.I. resulted. In a no-choice situation, ethanol intake was increased only on the first day of each intermittent incorporation of CDP (3 days for each 6-day cycle), being more persistent in group B (2 to 15% ethanol) than in group C (2 to 6.5%). Ethanol intake decreased in group C when alcohol concentrations exceeded 10%. The “first-day” CDP effect also occurred in the no-choice situation of an ethanolic liquid diet. Possible factors for this effect are discussed. Thus the effects of CDP on alcohol consumption in non-deprived mice vary with experimental designs.     

Comparative study of retrograde amnesia in rats on active and passive avoidance tasks and spontaneous recovery of memory

Naive and pretrained rats were trained in two active avoidance paradigms using a pole-climbing box and in a single-trial passive avoidance task using a T-maze. They were then subjected to amnestic treatments with electroshock, leptazol, pentobarbitone, or ether anesthesia. Single retention tests were given at 20–24, 44–48, or 68–96 h postreatment. Electroshock and leptazol seizures produced retrograde amnesia in all three paradigms, provided that seizures were maximal and retention was tested before 48 h. Prior treatment with anticonvulsant drugs prevented amnesia. Ether and pentobarbitone anesthesia failed to produce amnesia in all three tasks. A trend of recovery from amnesia was observed in the electroshock and leptazol groups when tested for retention 48–96 h posttreatment. On the other hand, the nonamnesic control, pentobarbitone, and ether groups showed signs of forgetting at these longer intervals. Consolidation failure and/or retrieval block was surmised to be the cause of amnesia; recovery was the possible result of removing the block.     

Determinants of alcohol use in pregnant women at risk for alcohol consumption

The purpose of this investigation was to identify determinants of alcohol consumption based on a number of demographic and psychosocial variables in a group of pregnant women at risk for alcohol consumption. Data were collected on a sample of 232 pregnant females who agreed to participant in a multistate alcohol prevention intervention. The variables of interest included demographic measures of race, age, education, marital status, health status, employment status and if they had been involved in physical abuse during the past year. Additionally, psychosocial variables were collected on social support, family functioning, mental health and illicit drug use. The dependent variables of interest were any alcohol use during the pregnancy and an abuse measure that was based on a composite score generated from questions related to problems associated with alcohol behavior. Logistic regression analysis was conducted to see if the independent variables (demographic and psychosocial variables) were predictive of any alcohol use. Multiple linear regressions were conducted to ascertain if the independent measures were predictive of alcohol abuse. The results showed that race, age, physical abuse and to a lesser extent health were associated to any alcohol use and alcohol abuse. The findings with the psychosocial variables were not as robust. Nevertheless, problematic psychiatric and drug use composite scores were associated with alcohol abuse.     

Divergent drinking patterns and factors affecting homemade alcohol consumption (the case of Russia)

BackgroundUnrecorded homemade alcohol consumption has been less examined in the literature. Previous studies of homemade alcohol in Russia have almost entirely focused upon the use of samogon (moonshine) attributed to the northern style of drinking. No systematic analysis is available regarding the production and consumption of homemade wine. This paper explores the drinking patterns demonstrated by consumers of samogon and homemade wine in Russia. The main factors affecting the consumption of these beverages are investigated.MethodsData were collected from a 2014 nationwide survey of 14,986 respondents aged 15+ years. Beverage preferences, volume of consumed alcohol, drinking habits, and alcohol availability were the main measures reported. Demographic, socio-economic, spatial, and policy-related factors affecting homemade alcohol consumption are examined using logistic regression.ResultsThe percentages of samogon and homemade wine consumers were similar, although a greater volume of samogon in pure alcohol was consumed compared to homemade wine. The groups of samogon and homemade wine consumers showed very little overlap. Unlike homemade wine consumers, samogon drinkers consumed larger amounts of alcohol and were more engaged in frequent and excessive drinking, drinking without meals and drinking in marginal public settings. Gender, education, regional affiliation, and type of residence showed opposite associations with regard to the consumption of samogon and homemade wine. Availability of homemade alcohol in the neighbourhood was the most influential predictor due to respondents’ own production, presence of homemade alcohol in friendship networks and at illegal market. The prices of manufactured alcohol and the consumption of homemade alcohol did not show significant relationships.ConclusionConsumers of samogon and homemade wine demonstrate contrasting drinking patterns that are largely driven by different factors. Samogon is consumed in a more hazardous manner, whereas homemade wine is consumed in a more moderate and law-abiding way. Illegal commercial samogon should be a special concern for alcohol policy.     

Inhibition of nitric oxide formation reduces voluntary ethanol consumption in the rat

Brain nitric oxide is involved in the mechanisms that regulate ingestive behaviour. To test whether this compound plays a role in alcohol preference, we studied the effects of different doses ofN ^G-nitro-L-arginine (L-NO arg), an inhibitor of nitric oxide synthase (NOS), on voluntary consumption of ethanol and on blood alcohol levels produced by a single intraperitoneal dose of alcohol in the rat. L-NO arg produced a significant and dose-dependent reduction of ethanol intake (P<0.001) without influencing total fluid consumption or feeding behaviour. L-NO arg did not influence the kinetics of alcohol. Our data show that inhibition of nitric oxide formation accompanies reduction of ethanol intake and suggest a possible role for nitric oxide in ethanol self-administration.     

Effects of alcohol consumption during pregnancy on subsequent maternal behaviour in rats

Nine Holtzman rats were maintained from days 5-18 of pregnancy on a liquid diet of which ethanol constituted 35% of the calories while nine rats were pair-fed an isocaloric diet that had maltose-dextrin substituted for the ethanol. Beginning on day 19 of gestation and continuing for five days the dams in both groups were given a choice among lab chow, water, and their respective liquid diets. During the five days of choice, alcohol consumption dropped to approximately 20% of pre-choice levels. The dams and pups showed no behavioural withdrawal symptoms. While the alcohol-treated litters showed greater variability in litter size and more pup deaths during nursing, the maternal behaviour of the alcohol dams was essentially normal, with only their pup protectiveness being rated lower than that of the control dams.     

Residual effects of prolonged cannabis treatment on shuttle-box avoidance in the rat

Chronic oral administration of cannabis extract to rats was examined for its residual effects on shuttle-box avoidance learning. In experiment 1 avoidance learning was assessed in rats that had been tested previosly on other behavioral tests. Chronic treatment (3 months) facilitated the learning of shuttle-box avoidance in cannabis-treated animals relative to vehicle controls. In experiment 2 very similar results were obtained in naive rats. These and other residual effects of chronic cannabis treatment are similar to the effects of hippocampal lesions.     

The psychological benefits of moderate alcohol consumption: a review of the literature

A review of the literature on the positive psychological benefits of light and moderate alcohol consumption suggests the following: (1) Alcohol in moderate amounts is effective in reducing stress. This has been found in both physiologic and self-report measures. (2) Low and moderate doses of alcohol have been reported to increase overall affective expression, happiness, euphoria, conviviality and pleasant and carefree feelings. Tension, depression and self-consciousness have been reported to decrease with equal doses. (3) Low alcohol doses have been found to improve certain types of cognitive performance. Included here are problem-solving and short-term memory. (4) Heavy drinkers and abstainers have higher rates of clinical depression than do regular moderate drinkers. (5) Alcohol in low and moderate doses has been effective in the treatment of geropsychiatric problems. As indicated in the text, results from many of the studies reviewed suggest that light or moderate drinking may be beneficial to psychological well-being. Liber (N. Engl. J. Med., 310(13) (1984) 846) has commented that the subject of control of alcohol intake evokes strong emotional responses, which can overshadow a logical assessment of whether or not to include 'healthy' drinking in a dietary plan. It is hoped that this review of data from available research can help provide a basis for making such an assessment.     

Preference for alcohol evoked by tetrahydropapaveroline (THP) chronically infused in the cerebral ventricle of the rat

The voluntary preference for ethyl alcohol in Sprague-Dawlet rats was determined over 12 days with water as the alternative fluid. The alcohol solutions offered to the animals were increased systematically in concentrations from 3 to 30%, according to a three-bottle, two-choice technique. Tetrahydropapaveroline (THP), a tetrahydroisoquinoline derivative, was infused repeatedly into the lateral cerebral ventricle of each rat through a guide tube implanted chronically. The metabolite was dissolved in a CSF vehicle, and infused in a volume of 1.0 μl every 15 min or 4.0 μl every 30 min around the clock, for the entire 12-day period of alcohol-water self-selection. Within 3 to 6 days of the start of infusion, extraordinary amounts of alcohol were consumed which ranged as high as 8 to 17 g per kg per day. Both the racemic mixture of THP and the S-(-)-THP isomer exerted this alcohol-inducing effect, when they were infused chronically in a range of doses from 100 picograms/μl to 1.0 mu;g/μl. Control intraventricular infusions of CSF according to the same regimen had no effect on alcohol preference. The excessive intake of alcohol during the intraventricular infusions of THP persisted long after the cessation of the infusion regimen, i.e., during retests carried out at one, six and nine months' intervals. Further, when THP-treated rats were offered a simultaneous choice of a palatable solution of saccharin together with alcohol, they continued to drink large volumes of alcohol. The 24 hr patterns of fluid intake, as registered continuously by a drinkometer, revealed that alcohol drinking was typically massed within two to four bouts during the night-time interval. During this period, the blood alcohol level reached concentrations as high as 0.2%. Withdrawal-like symptoms including wet-dog shakes, elevated tail, whisker twitching and occasional convulsive episodes, were also observed in the THP-infused rats. These findings provide support for the hypothesis that an alkaloid metabolite, which may be formed in both the brain and periphery, is involved in the mechanism underlying the pathological and sustained drinking which is characteristic of the disease state of alcoholism.     

Avoidance training in both alcohol and non-drug states increases the resistance-to-extinction of an avoidance response in rats

Three groups of rats were given avoidance training followed by extinction. One group received one acquisition session immediately followed by extinction. A second group received two acquisition sessions while in the non-drug state, followed by extinction. A third group received two acquisition sessions, one while under the effects of alcohol and the second under no-drug conditions, followed by extinction. The group trained under two drug states made significantly more responses than the other two groups, while the group which received two training sessions while undrugged also made more responses than the group which received a single session. The results indicated that an avoidance response trained under more than one drug state is more resistant to extinction than a response learned only in one drug state.     

Counting the cold ones: A comparison of methods measuring total alcohol consumption of managed alcohol program participants

Introduction and Aims

Managed alcohol programs (MAP) aim to reduce harms experienced by unstably housed individuals with alcohol use disorders by providing regulated access to beverage alcohol, usually alongside housing, meals and other supports. This study compares two methods of estimating participants’ outside alcohol consumption in order to inform program policies and practices around alcohol dosing and reducing risks of alcohol‐related illnesses.

Methods

The total alcohol consumption of 65 people participating in Canadian MAPs was assessed comparing daily MAP records (1903 client days) with researcher‐administered surveys over the same time period. A sub‐sample of more complete daily MAP records for 39 people (696 client days) was also compared with the equivalent survey data on drinking.

Results

Significantly more standard drinks per day (SDs, one SD = 17.05 mL ethanol) were reported in research interviews than recorded by program staff, whether for program administered drinks alone (means 16.04 vs. 8.32 SDs, t = 5.79, P < 0.001) or including outside‐program drinks as reported to staff (16.04 vs. 8.89 SDs, t = 5.37, P < 0.001). Consistent results were found in the sub‐sample. The number of outside drinks estimated by comparing program records with the research interviews, varied between 2.71 and 9.94 mean drinks per day per site.

Discussion and Conclusions

At two sites, MAP participants reported consuming more than twice the amount of alcohol administered on the program. At most sites, there was significant under‐reporting of outside drinking. Addressing the problem of outside drinking and total daily consumption is critical for achieving program goals of both short and long‐term harm reduction.

     

Shock induced alcohol consumption in rats: role of initial preference

In three experiments it was found that the effects of inescapable unavoidable shocks upon alcohol intake were dependent upon the initial preference displayed by the animal. When animals displayed a low initial preference for alcohol (Experiment 1) shock stress led to an increase in daily alcohol intake. When animals displayed a high initial preference for alcohol due to the addition of a preferred flavour (Experiment 2) or forced acclimation (Experiment 3) shock stress led to a decrease in daily alcohol intake. It is suggested that alcohol is consumed as a function of the punishing and discriminative properties of the shocks, not to alleviate stress through its pharmacological properties.     

The unique contribution of attitudes toward non-alcoholic drinks to the prediction of adolescents' and young adults' alcohol consumption

Attitudes toward alternative behaviors, such as drinking soda instead of alcohol, might contribute to the prediction of young people's drinking behavior. The current study explored the associations between late adolescents' and young adults' attitudes toward alcoholic and non-alcoholic drinks and their alcohol consumption, and whether these associations were moderated by participants' sex, age and education level. Cross-sectional data were collected among 1012 15 to 25-year-olds. Participants completed an online questionnaire on attitudes toward alcoholic and non-alcoholic drinks, binge drinking and monthly alcohol consumption.     

Effect of aluminum upon conditioned avoidance response acquisition in the absence of neurofibrillary degeneration.

Aluminum induces neurofibrillary degeneration in cats but not rats. Cats develop a progressive encephalopathy in which an early manifestation is impaired learning-memory performance. At brain aluminum concentrations of 5 to 6 times that found in cat, rats demonstrate an initial transient weight loss and acquisition deficit immediately following intracranial injection. However, rats do not develop a progressive encephalopathy or a chronic learning deficit.     

Emerging pharmacotherapies for alcohol dependence: A systematic review focusing on reduction in consumption

Background

European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption.

Methods

We searched PubMed and Embase (December 2001–November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n ≤ 20, were excluded. Studies were then classified as ‘abstinence’ if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as ‘reduction in consumption’.

Results

Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption.

Conclusions

While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence.     

Effects of RO 15-4513 and FG 7142 alone and in combination with ethanol on avoidance in the rat

Rats were trained on a complex avoidance schedule in which responses on one lever postponed shock and responses on another lever occasionally (variable-interval 45 sec schedule) produced 2 min periods of timeout from avoidance. As shown in previous experiments, ethanol (1.5 or 2.0 g/kg) produced an increase in timeout responding relative to avoidance lever rates. These effects were attenuated in five of the six rats by 6 mg/kg RO 15-4513, a dose that did not produce consistent intrinsic effects. In contrast, FG 7142 (10 mg/kg) reliably reversed ethanol effects in only one of the six rats tested. These results support the notion that RO 15-4513 possesses specific ethanol antagonist properties.     

Paternal alcohol exposure and hyperactivity in rat offspring: Effects of amphetamine

Locomotor activity of rat offspring sired by fathers treated with 0, 2 or 3 g/kg of alcohol twice daily was assessed at 21, 42 and 90 days of age. Fathers treated with the two lower doses were pair-fed to those treated with the highest dose. Offspring of nontreated ad-lib fed fathers were also evaluated to determine the possible role of paternal stress associated with intubation and pair-feeding. The behavioral response to amphetamine was also examined in 90-day-old male offspring. Paternal alcohol treatment resulted in increased activity at each age for 3 g/kg offspring compared to pair-fed controls. Ad-lib offspring did not differ from 0 g/kg controls at 21 and 42 days of age. The significant effect of paternal alcohol treatment on offspring activity at 90 days, including a significant linear paternal effect, occurred when all amphetamine-treated groups were pooled. The alcohol × amphetamine interaction was not significant, but a significant linear paternal alcohol × linear amphetamine interaction indicated that the paternal alcohol effect on activity was differentially responsive to amphetamine. Subsequent analysis of this interaction indicated a significant linear paternal alcohol trend only at the high dose of amphetamine. These results corroborate a previous report of increased activity on the part of offspring sired by fathers treated with alcohol. The presence of a differential effect of amphetamine suggests that the paternal effect on activity may be mediated by catecholaminergic activity. The absence of significant differences between ad lib and 0 g/kg pair-fed controls indicates that paternal stress/undernutrition does not significantly affect offspring activity.