Profiles of brain functional asymmetry in patients with alcoholism and drug addiction

Profiles of motor, sensory, and cognitive asymmetries in patients with drug addiction and alcoholism and in people of relevant control group were studied. To reveal the profiles of interhemispheric asymmetry, a set of tests for determination of lateralization of motor (the dominant hand and leg), sensory (eye and ear) and cognitive (right- and left-hemispheric mode of solution of verbal and/or spatial tasks) was used. In patients with drug addiction and alcoholism as compared with the control group, a statistically significant domination of the left-sided lateralization of motor and sensory indexes was found. The right-hemispheric mode was essentially prevailing in solving the verbal and spatial tasks. No differences in motor asymmetry were observed in narcotic addicts and alcoholics. The dominant left eye and ear were statistically significantly more frequent in patients with alcoholism than in patients with drug addiction. The right-hemispheric mode in solution of cognitive tasks was used more often statistically significantly by narcotic addicts than by alcoholics. The obtained data indicate an essential impairment of profiles of the motor, sensory, and cognitive asymmetries in patients with the chemical addiction.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 5, 2004, pp. 450–454.Original Russian Text Copyright © 2004 by Egorov, Tikhomirov.To the 100-Anniversary of N. N. Traugott     

Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking

Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development and symptoms, such as craving, loss of control, physical dependence, and tolerance, have been linked to changes in mesolimbic, mesocortical neurotransmitter systems utilizing biogenic amines, GABA, and glutamate. Identification of genes predisposing to alcoholism, or to alcohol-related behaviors in animal models, has been elusive because of variable interactions of multiple genes with relatively small individual effect size and sensitivity of the predisposing genotype to lifestyle and environmental factors. Here, using near-isogenic advanced animal models with reduced genetic background interactions, we integrate gene mapping and gene mRNA expression data in segregating and congenic mice and identify glutamate receptor metabotropic 7 (Grm7) as a cis-regulated gene for alcohol consumption. Traditionally, the mesoaccumbal dopamine reward hypothesis of addiction and the role of the ionotropic glutamate receptors have been emphasized. Our results lend support to an emerging direction of research on the role of metabotropic glutamate receptors in alcoholism and drug addiction. These data suggest for the first time that Grm7 is a risk factor for alcohol drinking and a new target in addiction therapy.     

Biochemistry for the benefit of humanity (practical achievements of my scientific work)

Science unites theory and practice, but theory is always in advance. Even our works (mentioned above) which are also important for practice and were awarded the State prizes could not be made without preliminary theoretical investigations. It should be said that our works with elaborated methods of therapy and drugs to treat chronic alcoholism, drug addiction, leucosis are rather of theoretical than of practical importance. Some our works which proved that carbon dioxide is the basis of life are also of especially great theoretical value. The paper deals with the investigations devoted to the problems of biochemistry in cattle breeding (the raising of fat content in milk; elaboration of the efficient method of fodder ensilage; raising of milk yield using the drug "Karboxilin"; development of the methods of isolation of crystalline glucose-oxidase and catalase used for clarifying blood) as well as to the problems of biochemistry in medicine (creation of the drug "Microcid", antileucosis drug "Corectin", drugs "Medichronal" and "Medicit" for treating alcoholism and drug addiction, drug "Namacit" for hindering the organism aging). Great attention is given to the problem of relations between the theoretical conception concerning the importance of CO2 in vital activity of human and animal organism and production of new drugs.     

Gender differences in chronic alcoholism: EEG analysis

Comparative analysis of spatial organization of cortical biopotentials of men (n = 120) and women (n = 75) suffering from alcoholism and persons without addiction to alcohol (control groups) was carried out. Gender differences in the EEG spatial parameters under study (linear spatial synchronization in the brain cortex, non-linear spatial disorder, EEG coherence, and spectral power) were shown to be markedly less pronounced between the control groups (68 women and 85 men) than between the alcohol addicts. The obtained data allow us to explain the known fact of more serious and "malignant" character of alcoholism in women than in men in terms of neurophysiology. In alcoholics, the synchronization of low-frequency oscillations (delta and theta) was higher, whereas the synchronization of the higher-frequency spectrum part (beta1 and beta2) was lower in women than in men. This fact can be a neurophysiological basis of more progredient inhibitory-degenerative processes in women.     

The treatment of perinatal addiction. Identification,intervention, and advocacy.

Women of reproductive age who use and abuse psychoactive drugs and alcohol present a special challenge to primary care physicians. There are compelling medical reasons for identifying and intervening with pregnant women who are addicted or have alcoholism. The teratogenicity of all drugs of abuse and alcohol, the risk of infection with the acquired immunodeficiency syndrome (AIDS), and the potential for full recovery of a pregnant woman from addiction are some of the reasons that identification and intervention in the problem are indicated. Whether encountered in the clinic setting or in private practice, chemically dependent pregnant or postpartum women are usually responsive to appropriate physician interventions that include a detailed and caring confrontation- and advocacy-oriented support. Complex legal and ethical issues surround perinatal addiction including the role of toxicologic screening, reports to child welfare services, issues in noncompliance, and interdisciplinary case management.     

Neurotransmitters in alcoholism: A review of neurobiological and genetic studies

Recent advances in the study of alcoholism have thrown light on the involvement of various neurotransmitters in the phenomenon of alcohol addiction. Various neurotransmitters have been implicated in alcohol addiction due to their imbalance in the brain, which could be either due to their excess activity or inhibition. This review paper aims to consolidate and to summarize some of the recent papers which have been published in this regard. The review paper will give an overview of the neurobiology of alcohol addiction, followed by detailed reviews of some of the recent papers published in the context of the genetics of alcohol addiction. Furthermore, the author hopes that the present text will be found useful to novices and experts alike in the field of neurotransmitters in alcoholism.     

Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury

Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC) and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions) and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure.     

药物成瘾的神经生物学机制研究

药物滥用既是全球普遍存在的公共卫生问题,又是危害严重的社会问题。药物成瘾的本质是一种以药物引起的基因表达和神经突触可塑性改变为基础的病理性记忆。主要介绍国内外近年的重要研究成果。     

Corticotropin-releasing hormone in the regulation of adaptive behavior

Recent findings on the role of corticotropin-releasing hormone (CRH) in the regulation of stress and its consequences are summarized and analyzed in the review. Being involved in stress-activating system this neurohormone is referred to as a neurochemical factor triggering and integrating both endocrine and behavioral functions. The CRH distribution in hypothalamus and extrahypothalamic brain regions relevant to its involvement in the controlling of endocrine processes and behavior is viewed in details. Distinct behavioral outcomes of stress and the contribution of amygdalar, hippocampal, and striatal CRH-structures, implicated in general organism response to external influences, are widely discussed. From this viewpoint the mechanisms involved in the development of post-stress psychopathology, as well as drug addiction and alcoholism are treated.     

THE USE OF ANTABUS IN THE THERAPY OF ALCOHOLIC PATIENTS

Preliminary studies on the effects of antabus (tetraethylthiuram disulfide) in the therapy of alcoholic patients indicate that it is very valuable in providing a “chemical foundation” for sobriety, even in those with a severe, long term drinking problem. In the first 30 patients treated, a favorable degree of control of the alcoholism has been effected in approximately 80 per cent. When taken regularly the drug maintains in the patient a very high degree of sensitivity to alcohol, quickly producing a number of very distressing bodily reactions whenever even very small amounts of spirits are ingested. Because of its potential dangers, antabus should be used only after thorough clinical and laboratory studies in properly staffed institutions. It is contraindicated in individuals with existing major psychosis or drug addiction and must be used only with caution in patients with diabetes mellitus, cardiovascular disease, goiter, pregnancy, epilepsy, asthma, and hepatic disease. Antabus therapy should be considered only one aspect of the total treatment program for the alcoholic patient.     

Transcriptional response to alcohol exposure in Drosophila melanogaster

Background  

Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance.     

HPA-axis activity in alcoholism: examples for a gene-environment interaction.

Genetic and environmental influences are both known to be causal factors in the development and maintenance of substance abuse disorders. This review aims to focus on the contributions of genetic and environmental research to the understanding of alcoholism and how gene-environment interactions result in a variety of addiction phenotypes. Gene-environment interactions have been reviewed by focusing on one of the most relevant environmental risk factors for alcoholism, stress. This is examined in more detail by reviewing the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and its genetic and molecular components in this disorder. Recent evidence from animal and human studies have shown that the effects of stress on alcohol drinking are mediated by core HPA axis genes and are associated with genetic variations in those genes. The findings of the studies discussed here suggest that the collaborations of neuroscience, psychobiology and molecular genetics provide a promising framework to elucidate the exact mechanisms of gene-environment interactions as seen to convene upon the HPA axis and effect phenotypes of addiction.     

Multiple parameter comparative EEG analysis in alcoholism and narcotic dependence

Multiparametric comparative analysis of spatial organization of EEG was carried out in 137 alcoholics and 131 heroin addicts. Common and different deviations from normal EEG (105 control subjects) were found. Global alterations of EEG spatial organization were observed in drug addicts (as compared to alcoholics). Such changes characterized increasing synchronizing effects of mesolimbic and brainstem structures on the brain cortex. The ethanol effects were more specific and asymmetric. Changes in EEG spectral-coherence characteristics were revealed in all frequency band, however, maximal changes took place in the high-frequency theta in drug addicts and in narrow-frequency alpha subranges in alcoholics. Different effects on the high-frequency EEG component (19.00-21.25 Hz) and information-energy index (coherence-to-spectral power ratio) suggest the difference influence of ethanol and heroin on emotional-motivational and cognitive processes as well as the level of consciousness. The obtained data on EEG discrimination of alcoholism and drug addiction (the inverse problem solution) on the basis of "specific" EEG patterns appear to have considerable promise in development of systems of occupational selection.     

Cdk5在可卡因诱导的药物成瘾中的作用

细胞周期素依赖性蛋白激酶5(cyclin dependent kinase-5,Cdk5)是细胞周期素蛋白激酶之一,具有很多磷酸化底物,其激动剂p35和p39特异存在于神经系统(CNS)。因此,Cdk5在神经系统中的功能尤为突出,成为神经科学研究热点。目前研究较多的是Cdk5在可卡因诱导的药物成瘾中的作用。在可卡因所致药物成瘾过程中,多巴胺系统,ΔFosB,神经元突触可塑性等发挥重要作用。Cdk5与这些分子相互作用,所以,Cdk5与可卡因诱导所致药物成瘾密切相关。阐明其与药物成瘾的联系,探索新的以Cdk5为靶向的药物,将可能成为成瘾治疗的有效手段。综述了在可卡因诱导的药物成瘾中Cdk5作用,以及Cdk5与相关的信号转导分子之间的相互调节。     

Pharmacogenetic approaches to the treatment of alcohol addiction

Addictive disorders are partly heritable, chronic, relapsing conditions that account for a tremendous disease burden. Currently available addiction pharmacotherapies are only moderately successful, continue to be viewed with considerable scepticism outside the scientific community and have not become widely adopted as treatments. More effective medical treatments are needed to transform addiction treatment and address currently unmet medical needs. Emerging evidence from alcoholism research suggests that no single advance can be expected to fundamentally change treatment outcomes. Rather, studies of opioid, corticotropin-releasing factor, GABA and serotonin systems suggest that incremental advances in treatment outcomes will result from an improved understanding of the genetic heterogeneity among patients with alcohol addiction, and the development of personalized treatments.     

药物成瘾及成瘾记忆的研究现状

本文在介绍药物成瘾与学习和记忆密切相关的神经回路及共同分子机制的基础上,围绕学习和记忆在药物成瘾中的作用,综述了关联性学习与复吸,关联性学习与敏化,异常关联性学习与强迫性用药行为,关联性学习及成瘾记忆与成瘾,多重记忆系统与成瘾的发生发展等方面的研究进展,并强调了突触可塑性及成瘾记忆在药物成瘾中的重要性。在此基础上提出：作为慢性脑病的药物成瘾的形成过程的重要特征是它包含着信息的特殊学习类型。药物成瘾与依赖于多巴胺的关联性学习紊乱有密切关系。海马可能在成瘾中扮演重要角色。     

HIV infection in pregnant women in Chelyabinsk

Data on HIV infection in pregnant women in Chelyabinsk are presented. Starting from 1999, a considerable rise in the number of HIV-infected persons was registered in this city. The social and epidemiological characteristics of HIV-infected pregnant women, as well as the main routes and factors of the infective agent transmission, are given. Relationship between the spread of HIV-infection and drug addiction is revealed. The occurrence of different opportunistic infections in HIV-infected pregnant women is determined.     

The prevalence of the use of narcotics and other psychoactive substances in Russia today

The epidemiological analysis of morbidity in drug addiction in Russia for the period of 25 years is presented. As shown in this analysis, by 1992 the number of drug addicts rose twofold in comparison with 1986, and by 1998 this number rose tenfold, reaching 109.5 per 100,000 of the population. The total number of persons given medical assistance on account of the abuse of narcotic and non-narcotic substances exceeded 295,000. The analysis states that the ratio of persons having problems with drugs and applying for medical assistance to the actual number of drug addicts is 1:7, i.e. the number of drug addicts among the population exceeds 2 million persons. The spread of drug addiction among adolescents, which grew eightfold during the last 10 years, is a particularly unfavorable phenomenon. The established tendencies towards the growth of morbidity rates in individual groups of population in Russia and the data obtained by questioning among the population are indicative of growth in the spread of drug addiction. This regularity is confirmed by the growing proportion of children, adolescents and women among those who applied for medical assistance for the first time.     

The monitoring of the spread of drug abuse as an element in the epidemiological surveillance of socially significant infections

The necessity of monitoring the spread of drug addiction in the system of epidemiological surveillance on HIV infection and parenteral virus hepatitides is shown. The results of the epidemiological diagnostics of registered drug addiction are presented. The criteria for the assessment of the epidemiological effectiveness of epidemiological surveillance on drug addiction are determined. As revealed in this study, during the period of 1991-1998 morbidity in drug addiction rose 57-fold in Perm Province, while the number of HIV-infected persons increased 75-fold. Pronounced direct relationship between the number of drug addicts, as well as persons belonging to groups of high risk of developing drug addiction, and the dynamics of morbidity in HIV infection and parenteral virus hepatitides B and C was established.     

Drug addiction: the neurobiology of behaviour gone awry

Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad "choices" that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction.