FORCED ALCOHOL INTAKE IN LABORATORY ANIMALS: METHODOLOGICAL ASPECTS OF ALCOHOL DEPENDENCE MODELING

AbstractThe abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder (AUD). An impaired ability to stop or control alcohol intake despite adverse health or social consequences characterize AUD. While AUDs predominantly occur in men, growing evidence suggests the existence of distinct cognitive and biological consequences of alcohol dependence in women. The molecular and physiological mechanisms participating in these differential effects remain unknown. Transcriptomic technology permits the detection of the biological mechanisms responsible for such sex-based differences, which supports the subsequent development of novel personalized therapeutics to treat AUD. We conducted a systematic review and meta-analysis of transcriptomics studies regarding alcohol dependence in humans with representation from both sexes. For each study, we processed and analyzed transcriptomic data to obtain a functional profile of pathways and biological functions and then integrated the resulting data by meta-analysis to characterize any sex-based transcriptomic differences associated with AUD. Global results of the transcriptomic analysis revealed the association of decreased tissue regeneration, embryo malformations, altered intracellular transport, and increased rate of RNA and protein replacement with female AUD patients. Meanwhile, our analysis indicated that increased inflammatory response and blood pressure and a reduction in DNA repair capabilities associated with male AUD patients. In summary, our functional meta-analysis of transcriptomic studies provides evidence for differential biological mechanisms that AUD patients of differing sex.Abstract Figure

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Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: Preliminary results of an open randomized study

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2008.08.019 ◽

2008 ◽

Vol 32 (8) ◽

pp. 1867-1872 ◽

Cited By ~ 12

Author(s):

Felice Nava ◽

Ezio Manzato ◽

Claudio Leonardi ◽

Alfio Lucchini

Keyword(s):

Maintenance Therapy ◽

Alcohol Dependence ◽

Alcohol Intake ◽

Randomized Study ◽

Heroin Addicts ◽

Preliminary Results ◽

Opioid Maintenance Therapy

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Alcoholism and Depression: Recent Results on the Mutual Interaction between Alcohol use, Stress-axis Dysfunction, and Affective Disorders

European Psychiatry ◽

10.1016/s0924-9338(09)70533-4 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

F. Kiefer ◽

K. Mann

Keyword(s):

Alcohol Dependence ◽

Alcohol Intake ◽

Plasma Concentrations ◽

Endocrine System ◽

Stress Axis ◽

Future Research ◽

Drinking Behaviour ◽

Suppression Test ◽

Coherent Body ◽

Anxiety Depression

Alcohol intake is known to modulate plasma concentrations of neuroendocrine peptides. However, recent results suggest that the endocrine system may not only respond passively to alcohol intake, but that -vice versa- it also actively modulates alcohol intake behaviour. The most coherent body of data concerns the hypothalamo-pituitary-adrenocortical (HPA) axis, with low corticotropin releasing hormone (CRH) being associated with more intense craving and increased probability of relapse after acute detoxification. It is important to bear in mind that dysregulation of the HPA system, as observed in alcohol dependence, is also a feature of anxiety and depression, two conditions which are frequently linked with alcohol dependence and have been reported to be associated with a poor prognosis. In depression, increased secretion of CRH seems to be one crucial mechanism. It has been found as a marker of depressive symptoms, which normalises when depression is successfully treated. Hypersecretion of CRH is associated with a general hyperactivity of the HPA system, notably elevated plasma levels of ACTH and cortisol, a blunted cortisol stress response and a blunted dexamethasone suppression test. In any case, HPA dysregulation, alcohol dependence, and depression are closely interrelated. Exactly which component of this triad is the driving force behind the various neuroendocrine correlates of drinking behaviour is currently unclear, and will need to be elucidated by future research. This will allow for an enlightened choice of potentially therapeutic agents for the treatment of co-morbid anxiety, depression, and alcohol dependence, acting primarily on the HPA system.

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Does comorbid depression and alcoholic dependence influence cognition in Bulgarian womеn?

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.546 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S473-S473

Author(s):

V. Giannouli ◽

D. Ivanova

Keyword(s):

Alcohol Dependence ◽

Alcohol Intake ◽

Depressive Symptomatology ◽

Statistical Significance ◽

Comorbid Depression ◽

Significance Level ◽

Self Reports ◽

Competing Interest ◽

The Impact ◽

Behavior And Cognition

IntroductionPrevious research on the impact of alcohol intake on human behavior and cognition has revealed the detrimental effects of alcohol dependence. Especially in women, depression is often associated with the initiation of alcohol abuse that provokes new episodes of depression and this cycle tends to chronify.ObjectiveAlthough the co-occurrence of depression and alcoholism is well documented, there is still scarce data on the cognition of depressed alcohol-depended women. The aim of the present study is to examine the cognitive function in women who demonstrate both depression and alcohol dependence.MethodA group of fifty-three Bulgarian women with a formal diagnosis of alcohol dependence (Mage = 43.89, SDage = 9.48; level of education: all with high school education) and varying levels of depressive symptomatology were examined at the Municipal Council on Drug Addiction Blagoevgrad. Information were collected from personal history taking (anamnesis), self-reports and the Lesch Alcoholism Typology–Questionnaire (LAT online program). The women were grouped according to their age (27–45 and 46–71).ResultsResults indicated that there is a significant influence of depression (P = .032), a slightly above the statistical significance level non-influence of age (P = .056), and an interaction of the influence of depression*age (P = .048) on self-reported cognitive performance.ConclusionsThe present research suggests that future researchers should further clarify in a more systematic way the factors that influence cognition in this special population with comorbid depression and alcoholic dependence.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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NEUROPROTECTIVE EFFECT OF SODIUM NITROPRUSSIDE INTRANASAL ADMINISTRATION ON FUNCTIONAL ACTIVITY OF THE BRAIN AND ANXIETY OF RATS WITH ALCOHOL DEPENDENCE

JOURNAL OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE ◽

10.37621/jnamsu-2020-1-2-1 ◽

2021 ◽

pp. 5-13

Author(s):

Anna Shlіakhova ◽

Elena Veselovska ◽

Olga Berchenko ◽

Anna Titkova ◽

Elena Prikhodko

Keyword(s):

Body Weight ◽

Alcohol Dependence ◽

Electrical Activity ◽

Sodium Nitroprusside ◽

Alcohol Withdrawal ◽

Baseline Level ◽

Intranasal Administration ◽

Alcohol Intake ◽

Paroxysmal Activity ◽

The Brain

Introduction. Disturbances of the molecular nitrosergic mechanisms of brain activity regulation underlie the reduction of brain protective functions under alcohol dependence. However, development of pathogenetically substantiated approaches to the correction of nitrogen oxide (NO) imbalance in the structures of the limbico-neocortical system of the brain (LNCSB) remains insufficient. Objective. To study the effect of intranasal sodium nitroprusside (SNP) administration on anxiety, electrical activity of the LNCSB and NO content in the hippocampus, hypothalamus and septum + nucleus аccumbens of rats with alcohol dependence. Materials and methods. The studies were carried out on 50 nonlinear white adult male rats in a chronic experiment in 3 groups: intact rats; rats with alcohol dependence; rats with alcohol dependence and intranasal SNP administration. The model of alcohol dependence was created by voluntary alcohol intake at a dose of 1.25 g/kg body weight of rat for 35 days. SNP was administered intranasal at a dose of 8 μg/kg body weight of the animal. The level of anxiety was determined by means of neuroethological tests: multi-parameter comprehensive assessment of anxiety, «open field» and «tail suspension test». The electrical activity of LNCSB was registered by the stereotactic introduction of electrodes. The concentration of NO was investigated in the hippocampus, hypothalamus, septum + nucleus аccumbens Results. Intranasal administration of SNP to rats with alcohol dependence led to suppression of convulsive and paroxysmal activity, caused by alcoholization and withdrawal of alcohol, on the electroencephalogram of the structures of the LNCSB and increased the absolute power of biopotentials of the delta and theta ranges on the spectrogram of the hippocampus. Reduction of anxiety was found in rats with a high baseline level of anxiety accompanied by recovery of NO level, which was depleted by chronic alcoholization, in the hypothalamus and hippocampus. Conclusions. Intranasal administration of SNP as a NO donor causes anxiolytic effects in the state of alcohol withdrawal depending on the baseline level of anxiety: in rats with the high baseline level of anxiety – reduces this level; in rats with the low baseline level – restrains it at the level of anxiety after alcohol intake. Intranasal administration of SNP to the rats with alcohol withdrawal causes positive changes in the electroencephalogram of the LNCSB, which are manifested in suppression of convulsive and paroxysmal activity and enhancement of brain biopotentials in alpha and delta ranges on spectrogram of hippocampus with sustaining this effect for whole day. Intranasal administration of SNP is a source of short-term supply of NO to brain cells, which leads to the restoration of NO levels in the hypothalamus, hippocampus, septum and nucleus accumbens – structures that are involved in the regulation of emotional motivational behavior. Key words. limbic-neocortical system of the brain, model of alcohol dependence, anxiety, nitric oxide, sodium nitroprusside

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Comparison of Disulfiram and Naltrexone in Cases of Alcohol Dependence Syndrome

Journal of Nepal Health Research Council ◽

10.33314/jnhrc.v18i1.1921 ◽

2020 ◽

Vol 18 (1) ◽

pp. 75-81

Author(s):

Sandarba Adhikari ◽

Pratikchya Tulachan ◽

Saroj Prasad Ojha ◽

Manisha Chapagai ◽

Saraswati Dhungana ◽

...

Keyword(s):

Alcohol Dependence ◽

Stages Of Change ◽

Alcohol Intake ◽

Psychological Intervention ◽

University Teaching ◽

Obsessive Compulsive ◽

Tertiary Institution ◽

Keywords Alcohol ◽

Alcohol Dependence Syndrome ◽

Approved Drugs

Background: Relapse prevention in alcoholism is recognised as an important component of management. Use of pharmacotherapies to prevent relapse in combination to psychological intervention is emerging. Disulfiram and Naltrexone are two of three FDA approved drugs for pharmacotherapy. The aim of the study is to compare the effectiveness of these two drugs in preventing relapse in alcohol dependence syndrome cases. Methods: A prospective crossectional study was conducted to compare disulfiram and naltrexone in alcohol dependent patients in tertiary institution. Cases of alcohol dependence syndrome were diagnosed based on ICD-10 DCR presenting to psychiatry department of Tribhuvan University Teaching Hospital, over the period of 6 months. After detoxification and fulfillment of inclusion criteria, semi structured proforma, Severity of alcohol dependence questionnaire, Stages of change readiness and treatment eagerness scale, Obsessive compulsive drinking scale were applied. Drug allocation was based on simple random method and on subsequent follow ups done at 2nd, 4th, 8th, 12th week semi structured proforma, Obsessive Compulsive Drinking Scale were completed and psychological intervention continued. After data collection, analysis and final results were computed.Results: Both drugs reduced craving (p<0.001) and amount of alcohol intake (p<0.001). Relapse was more in naltrexone group but was not statistically significant (p>0.05). Side effects were more with disulfiram (p<0.001) whereas dropout was more in naltrexone group, (p<0.01).Conclusions: Disulfiram and Naltrexone were equally effective in reducing craving, reducing amount of alcohol intake, and preventing relapse in 12 weeks follow up period. Naltrexone was found to be better in tolerability whereas disulfiram was better in terms of dropout from treatment. Keywords: Alcohol dependence; disulfiram; naltrexone; relapse

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Long-term pharmacotherapy aimed at maintaining abstinence or reducing alcohol intake in alcohol-dependent individuals. Guidelines from the Section of Pharmacotherapy of Polish Society for Research on Addictions (PTBU) and the Section of Psychopharmacology of Polish Psychiatric Association (PTP) – 2019 update

Pharmacotherapy in Psychiatry and Neurology ◽

10.33450/fpn.2019.10.003 ◽

2019 ◽

Vol 35 (2) ◽

pp. 95-110

Author(s):

Przemyslaw Bienkowski ◽

Marcin Wojnar ◽

Pawel Mierzejewski ◽

Jerzy Samochowiec ◽

Boguslaw Habrat ◽

...

Keyword(s):

Alcohol Dependence ◽

Alcohol Intake ◽

Scientific Debate ◽

Polish Society ◽

Practical Guidelines ◽

Alcohol Dependent

The article presents update of the 2013 Guidelines of the Pharmacotherapy Section of the Polish Society for Research on Addictions (PTBU) and the Psychopharmacology Section of the Polish Psychiatric Association (PTP) on long-term pharmacotherapy aimed at maintaining abstinence or reducing alcohol intake in adult alcohol-dependent patients. Apart from practical guidelines for long-term pharmacotherapy of alcohol dependence, the authors present the areas of uncertainty, which still require further studies and scientific debate.

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The controlled drinking controversy

Irish Journal of Psychological Medicine ◽

10.1017/s0790966700013033 ◽

1993 ◽

Vol 10 (2) ◽

pp. 121-123

Author(s):

John Tobin ◽

William Delaney ◽

Harry Doyle

Keyword(s):

Alcohol Dependence ◽

Data Base ◽

Treatment Option ◽

Alcohol Intake ◽

Social Attitudes ◽

Treatment Model ◽

Collateral Information ◽

Controlled Drinking ◽

The Social ◽

Viable Treatment

AbstractObjective:of the review was to explore the three major controversies over the controlled drinking debate, and to assess for whom controlled drinking may be a viable form of treatment of alcohol dependence.Method:was to survey the literature of the last twenty years, using the Medline data base, the Index Medicus, and the Excerpta Medica.Findings:were that controversies involving the work of the Sobells and the Rand reports were influenced by the social attitudes of the time, and that D.L. Davies work despite being methodologically unsound, made the consideration of having a controlled drinking goal a viable treatment option. We also found that comparing studies using different definitions of controlled/normal drinking is difficult, but it would appear that the young, married, less severely dependent, and possibly female drinker may benefit from this form of treatment. The return of a patient to controlled drinking is not always dependent on the treatment model they have undergone.Conclusions:are that controlled drinking should be considered as a serious option, and that the recommended safe alcohol intake, will differ between patients, and that flexibility will be required. Also that a source of ongoing collateral information about the patient is essential.

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Biochemical and genetic markers in patients with alcohol dependence and affective disorders and their correlation with alcohol intake

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.821 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S19-S20

Author(s):

U. Preuss ◽

F. Wurst

Keyword(s):

Alcohol Use ◽

Alcohol Dependence ◽

Affective Disorders ◽

Alcohol Intake ◽

Bipolar Disorders ◽

Cross Sectional Study ◽

Emergency Rooms ◽

Higher Alcohol ◽

Cross Sectional ◽

Alcohol Dependent

Rates of comorbid affective disorders in alcohol-dependent individuals are significant. Biomarkers of alcohol use may support the diagnosis of high and frequent alcohol use in these individuals. The aim of these analyses of the WHO-ISBRA Study on State and Trait Markers of Alcohol Use and Dependence is to compare biomarkers of alcohol use across individuals with and without comorbid alcohol dependence and affective disorders. Significantly, higher values of these biomarkers are hypothesized in individuals with comorbid disorders compared to alcohol dependence only. Assessment of Alcohol dependence and comorbid depression and bipolar disorders were conducted using an adapted version of the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS). Altogether, n = 1863 individuals were included into the analyses, of whom n = 299 had a lifetime history of depression and n = 20 a bipolar disorder. Clinical characteristics like mean alcohol intake last month and biomarkers including ASAT, GGT, CDT, 5-HTOL/5-HIAA ratio and MAO-Activity were included into the analyses. Results indicate that AD only subjects had higher measures of all biomarkers compared to comorbid bipolar and depression subjects, while the latter had a higher alcohol intake during last month.Since this is a cross-sectional study, conducted in emergency rooms of several countries, this allegedly divergent result in alcohol intake in comorbid subjects compared to higher biomarkers in AD only subjects may indicate that drinking is more frequent in alcohol-dependent individuals while bipolar and depressed subjects may have more episodic pattern of alcohol intake. The latter may lead to shorter periods of intake compared to the chronic and frequent use of this substance in alcohol-dependent individuals and higher biomarkers of alcohol use.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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