Biomedical subjects

B Tabakoff

Publications and source records attributed to B Tabakoff.

239 records · Page 14Linked to original sources

PubMedDate not supplied

Ethanol and the NMDA receptor.

The actions of glutamate, the major excitatory amino acid in the CNS, are mediated by three receptor subtypes: kainate, quisqualate and N-methyl-D-aspartate (NMDA) receptors. Ethanol, in vitro, is a potent and selective inhibitor of the actions of agonists at the NMDA receptor. Following chronic ethanol ingestion, the number of NMDA receptor-ion channel complexes in certain brain areas is increased. This increase may contribute to the generation of ethanol withdrawal seizures, since administration of an NMDA receptor antagonist can reduce these seizures. The results suggest that certain acute behavioral effects of ethanol, such as effects on memory, as well as certain aspects of ethanol withdrawal, may involve the NMDA receptor.

Animals↗

PubMedDate not supplied

Biochemical markers of alcohol use and abuse: experiences from the Pilot Study of the WHO/ISBRA Collaborative Project on state and trait markers of alcohol. International Society for Biomedical Research on Alcoholism.

The development of reliable diagnostic tools for assessing alcoholism and harmful alcohol consumption is an utmost necessity for the success of efforts to prevent and treat alcohol-induced damage to both individuals and to society. A multinational study is underway to aid in the development of biological screening tools (state markers) which can, with good sensitivity and specificity, identify problem drinkers. To attain this goal information needs to be available on an individuals's drinking history and habits and related factors. A detailed instrument has been developed to obtain this information. The second goal of the study was to begin to develop diagnostic 'trait markers' which provide biological information on genetically determined predisposing and protective factors in the development of alcoholism. The developed questionnaire also provides background information on subject characteristics necessary for the development of trait markers. Centres will assay the obtained biological samples for 'traditional' and newly identified state markers of excessive alcohol consumption. These will include methanol measurements, gamma-glutamyltransferase, aspartate aminotransferase, carbohydrate-deficient transferrin, serotonin metabolite ratios, and erythrocyte aldehyde dehydrogenase. DNA obtained from the lymphocytes of subjects will be assayed for polymorphisms of alcohol- and aldehyde-metabolizing enzymes and dopamine receptor polymorphisms which can provide insights into protective and predisposing factors in alcoholism. The platelet enzymes, monoamine oxidase and adenylyl cyclase, will be assayed to assess the relationships between these putative trait markers and the genetic and environmental factors contributing to the aetiology of alcoholism. The current report is meant to introduce the study design and present a portion of the preliminary data gathered in the process of establishing this research programme.

Adolescent↗

PubMedDate not supplied

Studies on tolerance development in inbred and heterogeneous stock National Institutes of Health rats.

The rate of development of environment-independent tolerance was assessed in seven inbred strains of rats, in randomly bred Sprague-Dawley rats, and in the heterogeneous stock (HS) animals developed from the inbred strains. The results demonstrated significant differences in rates of tolerance development between the various groups of inbred animals. A relationship between the initial sensitivity of an animal to the incoordinating effects of ethanol and the rate of tolerance development was also demonstrated. Animals displaying the greatest initial sensitivity to ethanol were found to develop tolerance at a faster rate than those displaying greater resistance to the incoordinating effects of ethanol. The HS animals developed from the inbred strains were demonstrated to embody the full range of rates of tolerance development exemplified by the parental inbred strains.

Alcoholism↗

PubMedDate not supplied

Genetics and biological markers of risk for alcoholism.

Substantial scientific evidence has accumulated that both genetic and environmental factors predispose the development of alcoholism in certain individuals. Evidence has accumulated to indicate that alcoholism is a heterogeneous entity arising from multiple etiologies. The demonstrated role of genetics in increasing the risk of alcoholism has promoted the search for biological markers that could objectively identify individuals who are genetically predisposed to alcoholism. Identifying such markers could allow for early diagnosis, focused prevention, and differential and type-specific treatment of alcoholism. Promising markers have been provided by research in electrophysiology, endocrinology, and biochemistry. Recent advances in molecular genetics are offering prospects for direct analysis of the human genome to determine elements that provide predisposition to, and protection from, alcoholism. Recent advances in research and new knowledge gained by the alcoholism treatment community and the lay public are helping to diminish the societal damage caused by alcohol abuse and alcoholism and to change prevailing attitudes about them.

Adenylyl Cyclases↗

PubMedDate not supplied

Effects of ethanol on calmodulin levels in mouse striatum and cerebral cortex.

Chronic ethanol administration has previously been shown to produce alterations in cAMP metabolism in neural tissue. The current study investigated the role of calmodulin (CM) in mediating these effects of ethanol. The levels and subcellular distribution of CM in mouse cerebral cortex were not altered at 0, 8 or 24 hr following withdrawal of mice from chronic ethanol administration. It was also shown that 24 hr following withdrawal from chronic ethanol administration, cytosolic and membrane-bound CM levels were not altered in mouse striatal tissue. Administration of a single 3.5 g/kg dose of ethanol to mice similarly did not alter CM levels or the subcellular distribution of CM in striatum. Ethanol (in concentrations up to 750 mM) in vitro did not affect the concentration-dependent activation of striatal adenylate cyclase by calcium and CM. Our results suggest that alterations in cAMP metabolism that are produced by ethanol treatment are probably not due to modifications in cellular CM levels, nor does ethanol appear to alter the interaction of calcium and CM with adenylate cyclase in vitro.

3',5'-Cyclic-AMP Phosphodiesterases↗