Alcohol Consumption In Animals Research Articles

Possible association between the lrrk2 gene and anxiety behavior: a systematic literature review

Alterations to the LRRK2 gene have been associated with Parkinson’s disease and alcohol consumption in animals and humans. Furthermore, these disorders are strongly related to anxiety disorders (ADs). Thus, we investigated how the LRRK2 gene might influence anxiety in humans and mice. We elaborated a systematic review based on the PRISMA Statement of studies that investigated levels of anxiety in animal or human models with alterations in the LRRK2 gene. The search was conducted in the PubMed, Scopus, and Web of Science databases, and in reference lists with descriptors related to ADs and the LRRK2. From the 62 articles assessed for eligibility, 16 were included: 11 conducted in humans and seven, in mice. Lrrk2 KO mice and the LRRK2 G2019S, LRRK2 R1441G, and LRRK2 R1441C variants were addressed. Five articles reported an increase in anxiety levels concerning the LRRK2 variants. Decreased anxiety levels were observed in two articles, one focusing on the LRRK2 G2019S and the other, on the Lrrk2 KO mice. Eight other articles reported no differences in anxiety levels in individuals with Lrrk2 alterations compared to their healthy controls. This study discusses a possible influence between the LRRK2 gene and anxiety, adding information to the existing knowledge respecting the influence of genetics on anxiety.

Copaiba (Copaifera reticulata) oleoresin reduces voluntary alcohol intake in rats

ABSTRACT Copaiba oleoresin, extracted from the Copaifera reticulata tree, has been used as a remedy in popular medicine in the Brazilian Amazon for various purposes, including reducing drug abuse. Yet no studies evaluated the effect of repeated administration of copaiba oil on alcohol consumption in animals. To evaluate this effect, we divided adult male Wistar rats into a) an alcohol group in which the animals had free access to choose between two bottles: one containing alcohol solution (20%) and another containing vehicle solution (0.2% saccharin); and b) a control group with access to two bottles containing vehicle solution. Rats were free to drink 24 h per day, for 35 days. Daily alcohol consumption and weekly body weight gain and food intake were monitored. From day 22, half of the rats in each group received 600 mg kg-1 copaiba oleoresin and the other received vehicle, subcutaneously, once a day, for three days. On day 35, rats were evaluated in an open-field test. The results showed that copaiba oil decreased voluntary alcohol intake and preference between days 2 and 6 after the last administration. Copaiba treatment also decreased the food intake and body weight gain in both alcohol and control groups without changing behaviors in the open-field test. Therefore, copaiba oil was able to reduce voluntary alcohol consumption in rats and could be tested in humans as an adjuvant to treat alcohol use disorder.

Investigations on the new mechanism of action for acetaldehyde-induced clastogenic effects in human lung fibroblasts

Acetaldehyde (AA) has been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC, WHO) and by the US Environmental Protection Agency due to its ability to cause tumours following inhalation or alcohol consumption in animals. Humans are constantly exposed to AA through inhalation from the environment through cigarette smoke, vehicle fumes and industrial emissions as well as by persistent alcohol ingestion. Individuals with deficiencies in the enzymes that are involved in the metabolism of AA are more susceptible to its toxicity and constitute a vulnerable human population. Studies have shown that AA induces DNA damage and cytogenetic abnormalities. A study was undertaken to elucidate the clastogenic effects induced by AA and any preceding DNA damage that occurs in normal human lung fibroblasts as this will further validate the detrimental effects of inhalation exposure to AA. AA exposure induced DNA damage, involving DNA double strand breaks, which could possibly occur at the telomeric regions as well, resulting in a clastogenic effect and subsequent genomic instability, which contributed to the cell cycle arrest. The clastogenic effect induced by AA in human lung fibroblasts was evidenced by micronuclei induction and chromosomal aberrations, including those at the telomeric regions. Co-localisation between the DNA double strand breaks and telomeric regions was observed, suggesting possible induction of DNA double strand breaks due to AA exposure at the telomeric regions as a new mechanism beyond the clastogenic effect of AA. From the cell cycle profile following AA exposure, a G2/M phase arrest and a decrease in cell viability were also detected. Therefore, these effects due to AA exposure via inhalation may have implications in the development of carcinogenesis in humans.

LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice.

There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls (p = 0.0035), as was ethanol preference (p = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administration. No significant effects on ethanol consumption or preference were observed in mice treated with 25 μg/kg LSD. Neither total fluid intake nor locomotor activity in the LSD-treated groups differed significantly from controls. These results suggest that classical hallucinogens in the animal model merit further study as a potential approach to the identification of targets for drug discovery and investigation of the neurobiology of addiction.

New Approaches to the Treatment Alcohol Addiction in Experimental Alcoholism

Studying the effects of drugs on neuronal GABA A /benzodiazepine receptors can be the basis to develop new approaches to the treatment of this disease. Wistar rats (n = 250) used in the experimental model of alcoholism. Properties of BDR 'synaptosomal” and 'mitochondrial” types were examined in respective membrane fractions obtained from brain cortex of rats with experimental alcoholism and treating of anticonvulsant meta-chloro-benzhydrylurea (m-chBHU) by radioreceptor assay with [ 3 H]flunitrazepam and [ 3 H]Ro5-4864. As a result of screening in terms of consumption of 15% alcohol and water in the rat were divided into 3 groups of animals. 1st – rats preferred to ethanol in testing – 'heavy drink” rats (15% alcohol as the sole source of drinking for 10 months); 2nd – rats preferred to ethanol – 'non-heavy drink” male contained no access to the entire period of ethanol; 3rd – 'non-prefer” alcohol rats – contained in the water. Introduction of m-chBHU rats 100 mg/kg for 14 days caused a significant decrease in alcohol consumption in animals preferring alcohol (1st and 2nd groups). Comparative study of kinetic parameters of selective ligands with bran membranes showed that properties of BDR in membranes from brain cortex of male rats with different preference to alcohol and showed that affinity of BDRs was decreased, but capacity of receptors was increased in brain cortex of 'heavy drink” and 'non-heavy drink” male rats compared with 'non-prefer” alcohol rats. Administration of m-chBHU induced mediation of GABA in brain of these rats and reduced alcohol consumptions.

P.1.g.051 Benzodiazepine receptor system in the brains of rats with experimental alcoholism and treatment effect of a novel anticonvulsant

Purpose: Alcohol abuse induces neuroadaptive alterations in the benzodiazepine receptors (BDR) that modulate GABAAR and GABA mediation in brain regions associated with reward function, producing alcohol addiction. Studying the effects of drugs that have modulatory effects on neuronal receptors, in particular the GABAA-benzodiazepine receptors, can be the basis for understanding the formation of alcohol motivation and addiction, to develop new approaches to the treatment of this disease. Materials and Methods: Male Wistar rats (n = 250) were used in an experimental model of alcoholism. Properties of BDR ‘synaptosomal’ and ‘mitochondrial’ types were examined in respective membrane fractions obtained from brain cortex of rats with experimental alcoholism and treatment with the novel anticonvulsant meta-chlorobenzhydryl urea by radioreceptor assay (RRA) with [3H]flunitrazepam and [3H]Ro5-4864. Results: Based on their consumption of 15% alcohol and/or water, the rats were divided into 3 major groups. Group 1 consisted of rats drinking ethanol only − these ‘heavy drinking’ rats had chronic alcoholism (15% alcohol as the sole source of drinking for 10 months); the second group consisted of rats preferring ethanol − these ‘non-heavy drinking’ rats drank mostly ethanol; the third group − ‘non-preferring’ rats − drank water mostly. In each group, a number of animals were administered meta-chlorobenzhydryl urea (m-CIBHU) 100mg/kg for 14 days. Introduction of m-CIBHU caused a significant decrease in alcohol consumption in animals preferring alcohol (1st and 2nd groups), by 82.7% from baseline and 75% from baseline, respectively (p< 0.05). Alcohol consumption by rats preferring water was not affected by m-CIBHU. Reduction of alcohol consumption started on the 2−3rd day of m-CIBHU administration, and persisted while on the drug and for 2 weeks after drug discontinuation. Thus, the introduction of m-CIBHU resulted in a significant reduction of ethanol intake for animals preferring ethanol. Comparative study of the kinetic parameters (Kd and Bmax) of [3H]flunitrazepam and [3H]Ro5-4864 binding with synaptosomal and mitochondrial membranes showed different properties of BDR in membranes from the brain cortex of rats with different preferences for alcohol: the affinity of [3H]flunitrazepam and [3H]Ro5-4864 binding with membranes was decreased, but capacity of receptors was increased, in the brain cortex of ‘heavy drinking’ and ‘non-heavy drinking’ rats compared with ‘non-preferring’ rats. Administration of the anticonvulsant meta-chlorobenzhydryl urea increased the affinity of BDR in the brain cortex of ‘heavy drinking’ rats, which induced mediation of GABA in the brain of these rats and reduced alcohol consumption. Conclusions: Our study revealed that the novel anticonvulsant meta-chlorobenzhydryl urea had a normalizing effect on GABAAreceptor function in ‘heavy drinking’ rats, and reduced alcohol consumption in these animals. P.1.g.052 Cariprazine demonstrates greater potency than aripiprazole in animal models of psychosis, cognitive impairment, and negative symptoms

Hypothesizing Darkness Induced Alcohol Intake Linked to Dopaminergic Regulation of Brain Function.

Understanding the role of neurotransmission in the prefrontal cortex and mesolimbic brain regions has become the subject of intensive neuroscience research worldwide. In the 1970s, our group provided evidence that rats exposed to darkness significantly augmented their alcohol intake. At that time, we proposed that melatonin was the culprit. At around the same time, our laboratory, amongst a few others, proposed that dopamine-adducts with acetaldehyde to induce alcohol intake both in rodents and in humans. While the work in these areas has declined considerably over the years, more recent scientifically sound studies continue to show the importance of these earlier controversial ideas involving alcohol abuse and alcoholism. A review of the literature has provided impetus to systematically access the newer genetic and molecular neurobiological findings relevant to the physiological and psychological motives for high alcohol consumption in animals and humans alike. Thus, we hypothesize that darkness-induced alcohol intake is linked not only to serotonergic-melatonin mechanisms, but also to dopaminergic regulation of brain mesolimbic pathways involving neuronal expression switching in response to long photoperiods affecting gene expression.

Social Interactions Affect the Ethanol Preference Forming in Rats

Model experiments with animals have showed that social relationships in communities of alcoholized animals are disturbed. The goal of this work was to study patterns of alcohol dependence development during individual alcohol consumption in animals housed in the groups where other members were not alcoholized in comparison to the groups of animals where all members were alcoholized. After 14 days of isolation 48 male Wistar rats were placed by 3 into standard cages. Hierarchical relationships between the rats were observed for the first 15 min after placing them into one cage. After three days of housing in groups the interactions between animals were studied again using the resident–intruder test. On the basis of the interactions recorded in all tests, the animal rank was determined. Studies were carried out in experimental groups of three types: 1) only one rat of each group was given 10% ethanol, whereas the other members received water. Such individual alcoholization was studied in animals of different hierarchical levels. 2) 10% ethanol was given to all animals living together. 3) all rats received water – control group. The level of alcohol preference was assessed in the “«two bottle» test” before and after 27 and 54 days of experiment. It was found, that social interactions significantly affect the development of ethanol preference in rats. Initial high anxiety level as well as subordinate and subordinate ranks predispose to ethanol intake. In groups of drinking together rats ethanol preference develops significantly higher than in case of drinking alone rat housed with alcohol free cage mates. Housing of drinking alone rat with alcohol free rats induces the aversive reaction to ethanol instead of their rank status.

Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers

There is an extensive literature showing that the CB(1) cannabinoid receptor antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers. In this study, 49 nontreatment-seeking heavy alcohol drinkers participated in a 3-week study. After a 1-week baseline, participants received either 20 mg/day of rimonabant or placebo for 2 weeks under double-blind conditions. During these 3 weeks, participants reported their daily alcohol consumption by telephone. Subsequently, they participated in an alcohol self-administration paradigm in which they received a priming dose of alcohol followed by the option of consuming either eight alcohol drinks or receiving $3.00 for each nonconsumed drink. Endocrine measures and self-rating scales were also obtained. Rimonabant did not change alcohol consumption during the 2 weeks of daily call-ins. Similarly, the drug did not change either alcohol self-administration or endocrine measures during the laboratory session. We conclude that the daily administration of 20 mg of rimonabant for 2 weeks has no effect on alcohol consumption in nontreatment-seeking heavy alcohol drinkers.

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.

Cue-induced behavioural activation: a novel model of alcohol craving?

Alcohol-associated cues elicit craving in human addicts but little is known about craving mechanisms. Current animal models focus on relapse and this may confound the effect of environmental cues. OBJECTIVES. To develop a model to study the effects of environmental cues on alcohol consumption in animals not experiencing withdrawal or relapse. Rats were trained to orally self-administer an alcohol (5% w/v)/saccharin (0.2%) solution 30 min a day for 20 days. After stable responding on a free choice between alcohol/saccharin and water, rats were exposed to 5, 10 or 15 min of alcohol-associated cues or 5 min of non-alcohol associated cues. The effect of a 5-min cue was measured after a 10-day break from training or pre-treatment with 0.03, 0.1 or 1 mg/kg naltrexone. Rats given 5 min of alcohol-associated cues responded significantly more on the active lever (26% increase) and consumed more alcohol as verified by increased blood alcohol levels (8.9 mM versus control 7.5 mM). Ten or 15 min of cues did not change alcohol consumption and 5 min in a novel environment decreased response by 66%. After a 10-day break in training, 5 min of alcohol-associated cues still increased alcohol consumption (29% increase) and the cue effect could be dose-dependently blocked by naltrexone (143% decrease at 0.03 mg/kg). Cue-induced behavioural activation was specific to alcohol cues, reproducible, persistent and could be blocked by naltrexone, and its correlation with human self-report of craving makes it a potentially useful model for studying alcohol craving.

Introduction to personality-biological interactions in alcoholism: 'The Markku Linnoila Memorial Symposium'.

Although a number of specific personality disorders, including anti-social personality, passive-dependent personality, and explosive personality, have been associated with the diagnosis of alcoholism, studies of the relationship of underlying personality and/or temperament to the nature, phenomenology, psychobiology, prognosis, and treatment of alcoholism have occurred much less frequently. However, there is a growing body of evidence that core or underlying personality and temperament are important determinants of vulnerability to becoming an alcoholic and of the nature of alcoholic subtypes. Furthermore, these personality and temperament variables appear linked to biological and/or genetic mechanisms. In parallel to human studies, experiments using rodents and primates have demonstrated animal behavioural characteristics, such as impulsivity, excessive or deficient behavioural inhibition, and a tendency to explore, which appear to parallel human personality characteristics, and these characteristics may predict genetically determined excessive alcohol consumption in animals. This special section is devoted to the memory of our esteemed colleague, Dr Markku Linnoila, honouring his many contributions to the field of alcoholism research and specifically to the theme of this special section. It is derived from a symposium presented at the Ninth Congress of the International Society for Biomedical Research on Alcoholism (ISBRA), held during the period 27 June‐2 July 1998 in Copenhagen, Denmark. As a world renowned expert on serotonin, Dr Linnoila led a team that was widely recognized as the world’s leading research group investigating serotonin and behaviour. His work was particularly focused on the relationship between serotonin and personality and he published numerous papers showing a relationship between the two. His 1983 landmark research paper investigating serotonin, fire-setting, and violence, bridged three disparate research fields: suicide, alcoholism, and aggression, and showed that the common link between these serotonin-mediated psychopathologies was impulsivity. While pursuing cutting-edge research with scientists in his homeland of Finland, where he was able to investigate the biological correlates of personality in violent offenders and alcoholics, he forged a relationship with those who were investigating non-human primate personality, leading to the first comprehensive non-human primate model linking serotonin and psychopathology. This model has been instrumental in understanding the biological and psychosocial correlates of Type 2-like excessive alcohol consumption. In this special section, we explore the interface

Opioid involvement in alcohol drinking.

A large body of evidence indicates that the endogenous opioid system plays an important role in maintaining alcohol drinking behavior. Evidence is reviewed that indicates that the reinforcing properties of alcohol that lead to continued and repeated bouts of drinking may be due, in part, to alcohol-induced activation of the endogenous opioid system. Much of this evidence is pharmacologic in nature. Blocking the action of endogenous opioid peptides via administration of opioid antagonists significantly attenuates alcohol consumption in animals under a variety of experimental conditions. In clinical trials, opioid receptor antagonists decrease alcohol consumption, relapse rates, subjective high, and alcohol craving in outpatient alcoholics. The potential clinical utility of opioid receptor antagonists in the treatment of alcoholism and alcohol dependence is discussed.

Social models of drinking behavior in animals. The importance of individual differences.

Although certain social environments clearly facilitate alcohol intake in humans, the role of social factors in alcohol consumption by animals is less clear. While social housing conditions such as crowding and isolation increase alcohol consumption in animals, in both cases this is mediated by heightened stress. Increases in social tension increase alcohol consumption in social groups of animals, but the literature is extremely variable in reports of how dominance correlates with alcohol consumption. Alcohol administration has biphasic effects on social behavior of animals similar to its biphasic effects on activity levels. We report a novel, social animal model of alcoholism. Rats raised over prolonged periods in highly enriched, social colony environments develop a variety of rhythms of alcohol consumption. But in each colony, only a few animals develop into extreme overconsumers of alcohol, and the proportion of colony-housed animals that develop such excessive alcohol -consumption habits is similar to the proportion of humans with alcohol problems. These overconsumers of alcohol from a rat colony show a variety of alterations in behavior, including chronic inactivity and low dominance standing. They represent a novel, voluntary animal model of social alcoholism.

Lithium in the Treatment of Other Psychiatric and Nonpsychiatric Disorders

In addition to its well-studied use in affective disorders, lithium has been evaluated in a wide variety of other psychiatric and nonpsychiatric conditions. There are over 150 published reports of lithium trials in approximately 30 different conditions. Placebo-controlled studies have failed to confirm claims of lithium effect in premenstrual tension 1-6 and have given negative results in obsessive-compulsive neurosis . 7-13 Ancedotal observations have indicated positive effects in anorexia nervosa, affective psychosis in organic brain syndrome, psychoses precipitated by drugs, pathological hypersexuality, and transvestism . 14-25 However, placebocontrolled studies are lacking. There have been 24 reports on the effects of lithium treatment on alcohol consumption in animals and man. 26-49 Of special interest here are the two recent double-blind, placebo-controlled trials, one American 35 and one British. 37 The American patients suffered from chronic alcoholism associated with nonpsychotic depression. Of the alcoholics finishing the trial, those given lithium had significantly fewer drinking

An Approach to the Use of Animal Models for the Study of Alcoholism&lt;subtitle&gt;A THEORETICAL REVIEW&lt;/subtitle&gt;

The use of animal models for the study of alcoholism is reviewed. Various types of models are described and the impact of different conceptual influences upon them together with their limitations are discussed. The commonly held view that animals, unlike man, are averse to drinking alcohol is questioned and it is maintained that alcohol consumption in animals and man is a complex subject which does not easily lend itself to such generalisations. The concept of ‘dependence’ is discussed with respect to its impact upon animal models. It is suggested that in this case semantic problems may act as a real barrier to the advance of research on alcoholism. Furthermore, an unnecessarily restrictive conceptualisation of ‘dependence’ as a unitary state results in a tendency towards the use of single measures of withdrawal-induced behaviour (e.g. withdrawal seizures) together with the administration of large doses of alcohol over a short period of time. Such procedures may often be counter-productive. A methodology is described in which detailed measurements of a wide range of physiological and behavioural events are made using animals which have voluntarily consumed low doses of alcohol. The role of social factors in animal models is also considered. It is suggested that underestimation of the complexity inherent in animal models could lead to inappropriate extrapolations of animal data to man.

Effects of Tetraethylthiuramdisulfide (Antabuse) on the Metabolism and Consumption of Ethanol in Mice

Acetaldehyde accumulation following ethanol administration and the effects of Antabuse on ethanol metabolism were studied in C57BL/CrgI and DBA/2Crgl mice. In alcohol preference tests, C57BL/Crgl mice consistently prefer alcohol to water, whereas DBA/2CrgI mice avoid alcohol. C57BL/Crgl mice were found to accumulate significantly less acetaldehyde than DBA/2Crgl mice following ethanol administration. Antabuse was found to increase acetaldehyde accumulation in both strains, but the effect was significantly greater in C57BL/Crgl than in DBA/2Crgl mice. Antabuse inhibited ethanol-l-1JC metabolism in mice of both strains, but again this effect was significantly greater in C57BL/Crgl than in DBA/2Crgl mice. The effects of Antabuse on voluntary ethanol consumption in C57BL/Crgl, RHI/Crgl, and C3H/Crgl mice was studied: Antabuse treatment decreased alcohol consumption in animals of all three strains.

Voluntary Alcohol Consumption in Animals: Peripheral and Intracerebral Factors

Voluntary Alcohol Consumption in Animals: Peripheral and Intracerebral Factors