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Biomedical subjects

G Freund

Publications and source records attributed to G Freund.

69 records · Page 4Linked to original sources
PubMed1970

Impairment of shock avoidance learning after long-term alcohol ingestion in mice.

Chronic alcohol consumption impaired the learning of a two-way shuttle box avoidance task in mice 10 to 14 days after the discontinuation of ethanol in the diet. Control groups received laboratory chow ad libitum or were pair-fed with the alcohol-consuming mice by diets containing isocaloric amounts of sucrose. The performance of the two control groups was indistinguishable from each other, and only the ethanol-consuming mice performed poorly. It was therefore concluded that alcohol consumption per se and not a nutritional deficiency was responsible for the impairment of learning.

Analysis of Variance↗
PubMedDate not supplied

Physical dependence on ethanol: conceptual considerations.

The mechanism of physical dependence is defined as a chain of events that begins at the physical level of membrane organization and that progresses through the various levels of biological organization to the behavioral level. An ethanol-induced alteration may be (1) cause, (2) effect, (3) an unrelated covariate of physical dependence, or (4) an experimental artifact. A variety of criteria in addition to correlation must be met before the significance of an ethanol-induced effect can be assessed. The reasons are summarized for assuming that physical effects of ethanol on membranes are the primary initiators of the cascade of events that leads to physical dependence.

Alcoholism↗
PubMedDate not supplied

Biomedical causes of alcohol abuse.

It is suggested that alcohol, like so many other drugs, is consumed for its rewarding and tension-reducing effects. The progression from use to abuse has many initiating and perpetuating causes at different levels of biological organization, ranging from the molecular to the behavioral level. The interactions between the many causes are better appreciated when they are conceptualized as originating at and progressing from one level to another. Among the perpetuating causes of alcohol abuse may be some of its consequences such as medical diseases and physical dependence. It is hypothesized that at the molecular level an acquired or inherited deficiency of anxiolytic synaptic receptors may be one of several causes of alcohol abuse.

Alcoholism↗
PubMedDate not supplied

Decrease of benzodiazepine receptors in frontal cortex of alcoholics.

We hypothesize that chronic alcohol abuse results in a loss of neurons and their associated synaptic receptors. This encephalopathy may be a precursor of brain atrophy and end-stage dementia. Autopsies were performed on normal brains of 27 alcoholics (mean age 62.5) and 30 nonalcoholic matched controls (mean age 64.4) free of other brain and liver diseases. None had recently received benzodiazepine medications. Gross brain atrophy was slight and equal in both groups. Benzodiazepine receptor densities and affinities in homogenates of frontal cortex were determined using [3H]flunitrazepam. Bmax specific binding was reduced by 20% in alcoholics compared with nonalcoholic controls of comparable age and with similar death-autopsy time intervals. The affinity was slightly less in the alcoholics. Wet tissue brain protein concentrations and their yields of 50,000-g pellet proteins were similar. Aging, death-autopsy time intervals, pneumonia and chronic obstructive pulmonary disease (diseases usually associated with hypoxia) had no significant effect on brain proteins, receptor densities, or affinities. We conclude that chronic alcoholism is associated with a loss of benzodiazepine receptor densities. Alcohol abuse may affect the results of post-mortem neurochemical investigations of other diseases.

Alcoholism↗
PubMedDate not supplied

Loss of muscarinic and benzodiazepine neuroreceptors from hippocampus of alcohol abusers.

Thiamine deficiency (Wernicke-Korsakoff's disease) may not be the only mechanism whereby chronic alcohol abuse affects the brain and not all alcohol-related changes may be evident morphologically. The purpose of this study was to determine if alcohol abuse affects muscarinic cholinergic and benzodiazepine receptors in the hippocampus of histologically normal brains obtained at autopsy in a general hospital population. Because patients were excluded who had significant brain atrophy and/or dementia severe enough to require institutionalization, the reported findings are presumed to be early changes in the development of an alcohol encephalopathy. In addition, patients were excluded from this study if they had clinical brain diseases (including Wernicke's disease), died in coma, had liver disease, or received medications that could potentially alter receptor binding. The reported changes in receptor binding were therefore presumed to be related to alcohol abuse per se and not an alcohol-associated condition. We found that muscarinic cholinergic synaptic receptor density determined with 3[H] quinuclidinyl benzilate was decreased by 30% in homogenates of the hippocampus of 25 alcohol abusers compared with 25 matched nonalcoholic controls. Similarly, densities of benzodiazepine receptors determined with 3[H] flunitrazepam were also decreased by approximately 30% in alcohol abusers. The affinities of both receptor types were not affected by alcohol abuse. Age and death-autopsy time interval had no significant effects on either wet tissue protein concentrations, yields of protein after centrifugation, or receptor binding. The contributions of age and time interval were each less than 2% of the total variance of protein concentrations and receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Alzheimer's disease and alcoholism: possible interactions.

The purpose of this investigation was to test the hypothesis that chronic exposure to alcohol may accelerate Alzheimer's disease (AD), either by independently adding receptor losses or by accelerating the AD disease process itself. Muscarinic [3H]quinuclidinyl benzilate and benzodiazepine [3H]-flunitrazepam receptor binding in homogenates of human autopsy brains were determined in four nonalcoholic and seven alcoholic AD brains and in histologically normal brains from 20 alcoholics and 20 nonalcoholics. Muscarinic binding was decreased in alcoholic AD compared with nonalcoholic AD in the parahippocampal region of frontal cortex, premotor temporal cortex, and amygdala, but not in the hippocampus. Benzodiazepine receptors were lost from the temporal cortex and amygdala, but the difference in the amygdala was not statistically significant. Plaque counts considered a marker of the severity of AD were not increased in the brains of alcoholics compared with nonalcoholics. Larger receptor losses in some alcoholic AD were associated with low plaque counts. Since all of these patients were severely demented, it is tentatively suggested that the receptor losses resulting from alcoholism may have contributed to the dementia in these AD patients.

Aged↗
PubMedDate not supplied

Apoptosis and gene expression: perspectives on alcohol-induced brain damage.

Apoptosis, genetically preprogrammed death of scattered cells, leaves few histological traces and is compatible with autopsy findings in brains of alcoholics. This type of cell death could be triggered by chronic exposure to alcohol. Interactions between alcohol and the activating and inhibiting molecular events of the apoptotic cascade could occur at several different levels. Sites of alcohol action could range from the transcription of the apoptosis genes to translation and posttranslational modifications of their protein products. The recent developments of in situ hybridization technology make it possible to determine the levels of the neurotoxic actions of ethanol and to detect early stages of toxicity where increased mRNA activity may compensate for losses of receptors, enzymes, peptide transmitters, or structural proteins. The potential for treatment with antisense nucleotides is discussed.

Alcoholism↗