Alter Alcohol Consumption Research Articles

Longitudinal Associations Between Smoking Cessation Medications and Alcohol Consumption Among Smokers in the International Tobacco Control Four Country Survey

Available evidence suggests that quitting smoking does not alter alcohol consumption. However, smoking cessation medications may have a direct impact on alcohol consumption independent of any effects on smoking cessation. Using an international longitudinal epidemiological sample of smokers, we evaluated whether smoking cessation medications altered alcohol consumption independent of quitting smoking. Longitudinal data were analyzed from the International Tobacco Control Four Country (ITC-4) Survey between 2007 and 2008, a telephone survey of nationally representative samples of smokers from the United Kingdom, Australia, Canada, and the United States (n = 4,995). Quantity and frequency of alcohol consumption, use of smoking cessation medications (varenicline, nicotine replacement [NRT], and no medications), and smoking behavior were assessed across 2 yearly waves. Controlling for baseline drinking and changes in smoking status, we evaluated whether smoking cessation medications were associated with reduced alcohol consumption. Varenicline was associated with a reduced likelihood of any drinking compared with nicotine replacement (OR = 0.56; 95% CI = 0.34 to 0.94), and consuming alcohol once a month or more compared to nicotine replacement (OR = 0.43; 95% CI = 0.27 to 0.69) or no medication (OR = 0.63; 95% CI = 0.41 to 0.99). Nicotine replacement was associated with an increased likelihood of consuming alcohol once a month or more compared to no medication (OR = 1.14; 95% CI = 1.03 to 1.25). Smoking cessation medications were not associated with more frequent drinking (once a week or more) or typical quantity consumed per episode. Medication effects on drinking frequency were independent of smoking cessation. This epidemiological investigation demonstrated that varenicline was associated with a reduced frequency of alcohol consumption. Continued work should clarify under what conditions nicotine replacement therapies may increase or decrease patterns of alcohol consumption.

Alterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission Tomography

A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release. The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer alpha-[(11)C]-methyl-L-tryptophan. Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala. Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation.

Efecto de la inhibición de la síntesis de angiotensina II en el consumo de alcohol

Central renin-angiotensin system modulates alcohol intake and inhibition of angiotensin converting enzyme reduces ethanol consumption in rats, and may be potentially useful in the treatment of alcoholism.To study the effect of captopril on alcohol intake, both in humans and animals .In a double-blind, placebo-controlled clinical study, 15 alcoholics who met DSM-IV criteria were randomized to receive captopril 100 mg/day or placebo for 12 weeks. In the experimental study, daily consumption of ethanol (10% v/v), water and solid food was assessed in 12 male Wistar rats before and after the intraperitoneal administration of captopril 50 mg/kg/day.In alcoholics, mean weekly standard alcoholic drink consumption was not different during captopril treatment or placebo. However, both groups had a significantly lower intake than during baseline. Days of abstinence increased and days of drunkeness decreased in the group receiving captopril, when compared with baseline but not with placebo. Craving was significantly reduced by captopril when compared with placebo. In rats, captopril reduced not only alcohol consumption but also water and food intake.Captopril decreases alcohol intake in rats and this effect is not specific for ethanol. Captopril did not alter alcohol consumption in alcoholics when compared with placebo but reduced craving.

Effect of angiotensin II synthesis inhibition on alcohol consumption

Central renin-angiotensin system modulates alcohol intake and inhibition of angiotensin converting enzyme reduces ethanol consumption in rats, and may be potentially useful in the treatment of alcoholism. To study the effect of captopril on alcohol intake, both in humans and animals . In a double-blind, placebo-controlled clinical study, 15 alcoholics who met DSM-IV criteria were randomized to receive captopril 100 mg/day or placebo for 12 weeks. In the experimental study, daily consumption of ethanol (10% v/v), water and solid food was assessed in 12 male Wistar rats before and after the intraperitoneal administration of captopril 50 mg/kg/day. In alcoholics, mean weekly standard alcoholic drink consumption was not different during captopril treatment or placebo. However, both groups had a significantly lower intake than during baseline. Days of abstinence increased and days of drunkeness decreased in the group receiving captopril, when compared with baseline but not with placebo. Craving was significantly reduced by captopril when compared with placebo. In rats, captopril reduced not only alcohol consumption but also water and food intake. Captopril decreases alcohol intake in rats and this effect is not specific for ethanol. Captopril did not alter alcohol consumption in alcoholics when compared with placebo but reduced craving.

Alcohol intake in high alcohol drinking (HAD) rats is suppressed by FG5865, a novel 5-HT 1A agonist/5-HT 2 antagonist

Both the 5-HT 2 antagonist, FG5606 (amperozide), and the mixed 5-HT 1 agonist/5-HT 2 antagonist, FG5893, attenuate significantly the volitional intake of alcohol in the cyanamide treated rat. The purpose of the present study was to investigate the effect on alcohol drinking in the selectively bred, high alcohol drinking (HAD) rat of a new and novel 5-HT 1A agonist/ 5-HT 2 antagonist, FG5865 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-l-piperazinyl]-3-pyridinecarboxylic acid methyl ester), which shares pharmacological properties with FG5893. Initially, a standard three bottle preference test for water vs. 3% to 30% alcohol solutions was given over 11 days to determine the maximally preferred concentration for each animal. Then water and this solution, which ranged between 9% and 20% with an overall mean absolute intake of 6.3 ± 0.5 g/kg per day, was offered over three consecutive 4-day test sequences: (1) predrug control; (2) SC injections b.i.d. of either 1.0 mg/kg or 2.5 mg/kg FG5865 or saline control vehicle; and (3) postdrug. Whereas saline failed to alter alcohol consumption of the HAD rats, FG5865 caused a significant dose dependent reduction by as much as 75% in the intakes of alcohol during its administration in terms of both g/kg ( p < 0.01) and proportion of alcohol to total fluid intake ( p < 0.01). During the administration of 2.5 mg/kg FG5865, alcohol drinking declined from 6.5 ± 0.3 g/kg to as low as 2.3 ± 0.2 g/kg per day. Neither the body weight of the HAD animals nor their intake of food was affected by either dose of FG5865. These results uphold the concept that the 5-HT 1A and 5-HT 2 receptor subtypes in the brain play a part in the aberrant drinking of alcohol of the HAD rat. Because FG5865 influences the activity of serotonergic neurons in the mesolimbic system of the rat, it is envisaged that the drug suppresses alcohol drinking by way of its action on these neurons.

Antidepressants suppress bulbectomy-induced augmentation of voluntary alcohol consumption in C57Bl/6j but not in DBA/2j mice

Bulbectomy has been previously shown to produce the specific antidepressant-sensitive syndrome in C57Bl/6j, but not DBA/2j mice. The present study examined the effect of the depression on voluntary alcohol consumption. Alcohol consumption and alcohol preference (% of alcohol solution in total liquid) in a free-choice, two-bottle situation was measured in C57BL/6j and DBA/2j mice after sham-operation, anosmia with 10% ZnSO 4, or bulbectomy. Both anosmic and bulbectomized mice of both strains consumed more alcohol and showed stronger preference for alcohol than sham-operated mice. In DBA/2j mice both operations altered alcohol consumption of the whole population, and the effect of bulbectomy was stronger. In C57Bl/6j mice bulbectomy and, to a less degree, anosmia seemed to affect predominantly the low-drinking animals. Chronic treatment with antidepressants amitriptyline (20 mg/kg), trazodone (20 mg/kg), and imipramine (10 mg/kg), did not change alcohol consumption in sham-operated C57Bl/6j mice. In anosmic mice antidepressants decreased alcohol preference, but only amitryptyline also decreased alcohol consumption. All antidepressants decreased both alcohol consumption and preference in bulbectomized C57Bl/6j mice. In DBA/2j mice antidepressant treatment either increased, or did not alter alcohol consumption and preference in all groups, though the effects varied among individual antidepressants. The possible connection between the bulbectomy-induced behavioral syndrome and elevated ethanol consumption in C57Bl/6j mice is discussed.

Effects of dopaminergic agents on alcohol consumption by rats in a limited access paradigm

The effects of several dopaminergic drugs on alcohol consumption were studied in free-feeding rats using a limited access paradigm. Ascending doses of amphetamine (0.1, 0.3 and 1.0 mg/kg), haloperidol (0.1, 0.3 and 1.0 mg/kg), SKF 38393 (a D1 receptor agonist - 0.3, 1.0 and 3.0 mg/kg), quinpirole (LY 171555, a D2 receptor agonist - 0.03, 0.1 and 0.3 mg/kg), SCH 23,390 (a D1 receptor blocker, 0.003, 0.01, 0.03 and 0.1 mg/kg) and spiperone (a D2 receptor blocker, 0.003, 0.01, 0.03 and 0.1 mg/kg) were administered IP to rats approximately 30 min prior to their 1-h per day access to alcohol. Each dose was administered for 5 successive days, and the effects of the drugs were compared to those of respective saline or 0.4% lactic acid solution controls. Although there was an overall significant dose effect of amphetamine on alcohol consumption, no single dose altered alcohol consumption significantly from baseline. SKF 38,393 specifically decreased alcohol consumption at the highest dose of 3 mg/kg. Quinpirole significantly increased water consumption at the highest dose but had no effect on alcohol consumption. The antagonist haloperidol decreased alcohol consumption but only at doses that also reduced water consumption. The specific antagonists SCH 23,390 and spiperone decreased water consumption at the highest doses tested without modifying alcohol consumption. Taken together, these data suggest that dopamine does not play as critical a role in mediating the reinforcing effects of alcohol (insofar as they are reflected by alcohol consumption) as it does in relation to other psychoactive drugs, particularly the psychomotor stimulants.

Systemic angiotensin II acts at the subfornical organ to suppress voluntary alcohol consumption

The subfornical organ plays a role in a number of the effects of blood-borne angiotensin II (ANG II) including the increase in water drinking and blood pressure and the release of vasopressin from the pituitary. Recently it has been shown that systemically administered ANG II also reduces voluntary alcohol intake. The present study assessed the role of the SFO in alcohol consumption by examining the effects of SFO lesions on voluntary alcohol intake and on the suppression of voluntary alcohol intake by ANG II. Whereas the lesion did not alter alcohol consumption per se, it did significantly attenuate the ability of ANG II to reduce alcohol intake. This effect was not due to a lesion-induced change in the pharmacokinetics of alcohol and was observed only in those animals whose lesions produced a functional deficit, i.e., abolishing the increase in water drinking produced by ANG II. These results indicate that the SFO mediates the effect of systemically administered ANG II on alcohol intake but does not otherwise affect the regulation of alcohol consumption.

Effect of chronic vasopressin treatment on alcohol drinking of Brattleboro HZ and DI rats

Preference for alcohol was determined for three groups of male and female rats, 100–150 days old, comprised of: (1) Long Evans (LE); (2) LE-derived Brattleboro heterozygous (HZ); and (3) Brattleboro homozygous (DI) animals afflicted with diabetes insipidus due to vasopressin deficiency. Each alcohol drinking test was run over 11 days during which food, water and an ethyl alcohol solution, increased in concentration from 3% to 25%, were freely available. Following an initial preference screen, 100 milli-units of vasopressin tannate in oil was administered subcutaneously, during a second preference test, once per day to each animal. This treatment ameliorated the polydipsia-polyuria syndrome characteristic of the DI sub-strain of Brattleboro rat. Administration of the peptide to both the LE or HZ animals exerted no effect on g/kg intake nor on the proportional measure of alcohol to water. However, in the DI rat of either gender, vasopressin reduced the mean absolute gram intake of alcohol over concentrations to resemble that of the other LE and/or HZ groups. These results demonstrate that vasopressin serves to normalize the intake of alcohol in the DI rat by virtue of the elimination of the diabetic condition. However, since vasopressin fails to alter alcohol consumption of the HZ and LE rats, it would appear that this neuroactive peptide may play only a minor role in the CNS mechanisms governing the voluntary selection of alcohol.

Effects of inescapable shock and shock-produced conflict on self selection of alcohol in rats

In five experiments it was found that stress of inescapable unavoidable shock produced increased self selection of alcohol. These effects were maintained only so long as the shock schedule was continued. Factors such as predictability of shock, shock schedule and nutritional deficiency were found not to alter alcohol consumption substanially. In contrast to the effects of inescapble unavoidable stress, shock-produced conflict did not lead tio the self selection of alcohol. Results were interpreted in terms of a Tension Reduction Hyothesis and the role of control over aversive stimulation.