Formation of experimental alcoholism in a population of crossbred rats

Experiments on random-bred rats were made to study the relationship between the duration of ethanol anesthesia and the time course of alcohol consumption for 8 months. Short-sleeping rats with ethanol anesthesia lasting less than 90 minutes exhibited initially high and steady alcoholic motivation. Meanwhile long-sleeping rats with ethanol anesthesia lasting over 175 minutes demonstrated high level of alcoholic motivation only under stressful conditions. After 8 months of keeping in isolated cages long-sleeping rats demonstrated the same intensity and steadiness of alcoholic motivation as was the case in short-sleeping animals. Long-sleeping rats differed from short-sleeping ones in hypersensitivity to the toxic action of ethanol. It is inferred that in random-bred rats, there are at least two forms of experimental alcoholism.     

Tyrosine hydroxylase activity in the brains of rats with different levels of initial alcoholic motivation

Activity and KM of hypothalamic tyrosine hydroxylase (TH) were studied in rats preliminarily tested for predisposition to high ethanol consumption. It was shown that as regards cofactor of DMPH4 enzymatic reaction, KM of hypothalamic TH of animals with an initially high alcoholic motivation is lower than that from the brain of animals rejecting alcohol, being 0.34 +/- 0.3 mM and 0.46+/- 0.10 mM, respectively. A conclusion is made that the catecholaminergic system is involved into the realization of the rewarding effects of ethanol.     

Splenopentin--modulator of immunological and behavioral reactions in secondary immunodeficiency state induced by experimental alcoholism

Effect of splenopentin on some patterns of immunity was studied in mice with chronic alcoholic intoxication. Splenopentin was administrated into animals once intraperitoneally (250 micrograms/kg). Administration of splenopentin was found to normalize several immunological patterns in animals with chronic alcoholic intoxication: the immune response to the thymus-dependent antigen sheep red blood cells and phagocytic activity of peritoneal macrophages. Also observations over C57B1/6 mice characterized by high level of alcoholic motivation showed that alcohol consumption in mice decreased after administration of splenopentin at a dose of 250 micrograms/kg during two weeks.     

Effect of the destruction of the brain serotoninergic system on the alcohol consumption by rats in the early periods of experimental alcoholism

Albino noninbred rats were divided into groups, according to the duration of alcoholic anesthesia (4.5 g/kg i.p.), of predisposed (195.6 min) and non-predisposed (69.1 min) to voluntary intake of alcohol. Another group included animals screened for 21 days according to the level of intake of 15% ethanol under the conditions of free choice between alcohol and water (6.15 and 2.62 g/kg pure ethanol per day, respectively). The animals were subjected to electro-coagulation of the dorsal or magnus raphe nucleus or were injected with 5,6-dihydroxytryptamine--DNT (75 micrograms/microliters) into the ventricles of the brain. It was established that in rats non-predisposed to alcohol intake, the destruction of the raphe nuclei, of the dorsal in particular, or injection of DOT to animals with a weak alcoholic motivation produces a dramatic increase in alcohol intake. In alcohol intake predisposed rats and in animals with a high level of alcohol use, analogous exposures do not bring about any significant differences in alcohol intake. The data obtained indicate that the reduced serotonin content in the brain is associated with an increase in the level of alcoholic motivation.     

Effect of septal damage on alcoholic motivation in the rat

Interconnection between predisposition to depressive-like state (DS) in stress situation and heightened addiction to ethanol was studied in nonlinear male white rats. Electrolytic lesion of the septum in animals inclined to the development of DS, led to a change from the passive type of reaction in stress conditions to the active type. The rate of formation of alcoholic motivation in these animals decreased in comparison with sham-operated rats. The effect of the septal lesion in rats with formed addiction to alcohol was less expressed. Conclusion is made that the passive type of reaction in extreme conditions is significant for the formation of alcohol motivation in rats, especially at early stages.     

The Medical Practitioner,Alcoholism and Motivation

Adverse influences on motivation for recovery from alcoholism must be searched for in three areas: society, the medical practitioner and the patient. Society is ambivalent because there is a vicarious release through identification with the cheerful “drunk” coupled with unconscious envy and resentment leading to punitive action.The current “alcohol culture” decrees that to drink is to be well, not to drink is to be ill.The medical profession attempts to suppress, deny, rationalize or reject the problem of alcoholism because it involves a change in attitude and recognition of limitations.The alcoholic patient has a notorious lack of motivation, but this must be recognized as a symptom of his disease, and with certain techniques this symptom is treatable. Furthermore, motivation fluctuates and many opportunities for treatment are available when the medical practitioner can detect that motivation is high. At times a coercive approach is required, at times a permissive one; and the optimal use of such approaches will increase the motivation to an effective level.     

Role of limbic-neocortical mechanisms in the formation of experimental alcoholism in the rat

The role of the amigdalar complex and the hippocampus as well as their interaction with the hypothalamus in a formation of attraction to alcohol was studied in 40 rats. After electrolytic lesions of the hippocampus and the amigdalar complex at early stages of alcoholization the inhibition of development of this pathologic attraction occurred however with subsequent dynamical reorganization of the structural and functional mechanisms of alcoholic motivation and with duplication of the triggering links. Important role of the limbico-neocortical relations was revealed in a development of behavioural and emotional-vegetative disturbances accompanying experimental alcoholism.     

Malic Acid Accumulation in Roots in Response to Flooding: Evidence Contrary to its Role as an Alternative to Ethanol

Across a time course of flooding the malic acid content in rootsof the swamp tree Nyssa sylvatica var. biflora increased 5-foldfrom 1 week to 1 month of flooding and remained at that levelthrough a full year of flooding. Alcoholic fermentation ratesaccelerated within the first month of flooding but dropped tovery low levels under long-term flooding. The theory that, underflooding, malic acid accumulates as an alternative anaerobicend product to ethanol is unlikely in this instance since (1)malate is initially associated with high alcoholic fermentationand (2) the reduction in alcoholic fermentation is accountedfor by increased internal aeration of the roots.     

Effect of psychotropic substances on the development of alcoholic motivation in noninbred white rats

The experiments have shown the capacity of antidepressant amitriptylin (0.5 mg/kg, i. p.) and tranquilizer phenazepam (0.1 mg/kg i. p.) to normalize the adaptive behaviour and almost completely prevent the development of alcohol motivation in animals with insufficient adaptive behaviour. It was established that in animals initially rejecting alcohol, chronic treatment with these drugs as well as d-amphetamine promoted alcohol motivation. The results obtained have proved our earlier hypothesis that preclinical search for drugs for the prevention and treatment of early stages of alcoholism is possible only in animals pre-selected according to their inclination to experimental alcoholism.     

Various features of the emotional behavior of animals with pronounced alcoholic motivation

Testing of animals with different degrees of manifestation of attraction to ethanol showed that in conditions of zoosocial conflict rats--potential dipsomaniacs have less competition abilities in their struggle for the aims of biological value as compared to the rats, who are not dipsomaniacs. Their failure in a conflict situation leads to the fact, that while getting in the same or some other stress conditions for the second time, the animal fully gives up activity and makes no attempts to overcome these situations. This weak behavioural activity of such rats is based on a great tendency to the development of depressive-like state. Alcohol in certain doses (0.5 g/kg) normalizes the behaviour of rats--potential dipsomaniacs. This, probably, explains the appearance of alcoholic motivation in these animals.     

Effect of ethanol on the concentration of enkephalins in the brain of rats with different levels of alcoholic motivation

Radioimmunoassay was used to measure the content of leu- and met-enkephalins in white random-bred rats divided into groups according to the duration of ethanol anesthesia and the levels of 15% ethanol consumption under the conditions of free choice. The concentration of neuropeptides was determined in the cortex of the large hemispheres, striatum, thalamus, and medulla oblongata. The short-sleeping animals manifested elevated concentration of leu-enkephalin in the cortex and that of met-enkephalin in the striatum, medulla oblongata, and thalamus. Prolonged alcoholization under the conditions of free choice led, in the much-drinking animals, to decreased concentration of leu- and met-enkephalins in the striatum, thalamus and medulla oblongata and to increased concentration of leu-enkephalin in the cortex. The importance of leu- and met-enkephalins in the pathogenesis of chronic experimental alcoholism in rats with different alcoholic motivation is considered.     

Parotid abscess due to salmonella enteritidis: A case report

BACKGROUND: Salmonella infection of the parotid gland is rare. CASE: An instance in a 50-year-old man of Salmonella enteritidis parotiditis initially recognized by microbial culture of a fine needle aspiration cytology material is described. The identified predisposing factor was chronic alcoholic abuse. For the infection source, a carrier state of salmonella parotitis was postulated, which progressed to focal abscess and was subsequently complicated by bacteremia and hematogenous spread to the liver, spleen and lungs. CONCLUSION: Salmonella should be included in the differential consideration of head and neck abscesses in immunocompromised individuals and treated aggressively.     

Neuroeconomics in parasitoids: computing accurately with a minute brain

In the so‐called ‘patch problem’, at any given moment, the forager must decide whether to leave the current patch or to remain there and continue foraging. Optimal foraging theory and subsequent theoretical works have identified theoretical optimal policies governing this decision. In a stochastic environment, the Bayesian framework has proved to be effective. A set of mechanistic proximal mechanisms explaining how parasitoid wasps may take decisions has been proposed. These mechanisms are based in on changes in the degree of motivation to continue foraging during a particular foraging episode. Using a simple, straightforward model, we show here that the psychological mechanism proposed mimics precisely the theoretical Bayesian solution, provided that motivation displays exponential decay, rather than the linear pattern of decay initially assumed. Changes in motivation thus function as a sort of analogue computer, and may be seen as more than purely heuristic rules of thumb. This link between psychological processes and ultimate optimisation places foraging theory in the domain of neuroeconomics.     

Role of dominant motivation in producing the effects of electric stimulation of hypothalamo-limbic structures

The experiments were made on cats with electrodes chronically implanted in the hypothalamus and the amygdala. The effects of electrical stimulation of the points from which the food reactions were initially evoked, were transformed into an avoidance reaction, if stimulation was applied in surroundings where the animals had previously received pain stimuli. Defensive reactions to stimulation of the hypothalamus and amygdala changed to alimentary reactions if the same stimulation was presented to hungry cats in conditions of repetitive feeding. A conclusion has been drawn that the elements of the hypothalamo-limbic structures have plastic properties and may be involved in different forms of behaviour, depending on current motivation and learning.     

Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption

Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body's retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption. A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minor RE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease.     

Interaction of ethanol with opiate receptors

Addition of ethanol to rat brain homogenate containing opiate receptors inhibits at a concentration of 50 mM the stereospecific binding of 3H-naloxone at 37 degrees C but not at 0 degree C, with the ID50 being 462 mM under these conditions. The temperature-dependent inhibition of the ligand binding suggests that ethanol does not compete with naloxone for specific binding sites of opiate receptors and changes the structure of lipids in biological membranes. Scatchard's analysis has demonstrated that apart from a decrease in the number of highly affinity binding sites of 3H-naloxone, the total amount of the binding sites remains unchanged both in the presence and absence of ethanol and constitutes 453 and 549 fmol/mg protein. It is assumed that ethanol might interconvert highly and low-affinity binding sites. Analysis of the effect of ethanol on 3H-naloxone binding with opiate receptors contained by synaptic membranes obtained from animals with varying predisposition to voluntary alcoholization has shown that ethanol inhibits to a greater degree ligand binding with membranes obtained from rats predisposed to alcoholization. The possibility of the involvement of receptors in the biochemical mechanisms by which the initial alcoholic motivation is effected is under discussion.     

Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn

Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract.     

Catecholaminergic and serotonergic correlates of formation of the morphine addiction in pubescent rats

Involvement of the catecholaminergic and serotonergic mechanisms in formation of morphine addiction was investigated in mongrel male pubescent rats. Involvement of the cerebral emotiogenic neurotransmitter systems in the morphine-induced reaction and subsequent suppression of the peripheral neurotransmission link resulting from repetitive morphine administrations are initially nonspecific. Neurochemical correlates of disadaptation in the pubescent age, which results in an early drug dependence, are discussed. This may be indicative of the existence of a special risk factor within this period of ontogenesis; this factor is responsible for the development of an artificially acquired motivation to morphine, which plays the role of a reinforcement agent for the system of positive emotional reaction.     

The response of skeletal muscle to alcohol abuse: Gender differences

A gender analysis has been carried out to analyze changes in intracellular signaling pathways that lead to the development of chronic alcoholic myopathy. It is known that acute or chronic alcohol intoxication can result in alcohol-induced lesions in skeletal muscles. Chronic alcoholic myopathy occurs much more frequently and can develop either independently or in combination with other forms of alcoholic disease (liver and heart lesions, malabsorption syndrome, or alcohol polyneuropathy). This disease is manifested by atrophy of skeletal muscles and a performance decrement. Most of the studies on the pathogenesis of chronic alcoholic myopathy have been carried out on male patients. Studies on alcoholic myopathy-induced muscle damage in females have not been previously reported.     

Level of delta sleep-inducing peptide (DSIP) in the brain of rats with different alcoholic motivation

Radioimmunoassay was used to measure the content of delta-sleep-inducing peptide (DSIP) in random-bred albino rats divided into groups according to the duration of ethanol anesthesia and the levels of 15% ethanol consumption under free-choice conditions. The concentration of the neuropeptide was assayed in intact brain, in the cortex of large hemispheres, medulla oblongata, thalamus and striatum. The short-sleeping rats manifested a statistically significant lowering of the DSIP content in intact brain homogenates, in the cortex of large hemispheres and striatum. On the contrary, thirty minutes after a single intraperitoneal injection of ethanol in a dose of 1 g/kg the DSIP content in the medulla oblongata, thalamus and striatum was found to be increased. The raising of the ethanol dose up to 2.5 and 4.5 g/kg was followed by a less significant increase in the neuropeptide content. Prolonged chronic alcoholization under free-choice conditions led after 12 months to the reduced DSIP content in the medulla oblongata, thalamus and striatum. The importance of DSIP for the pathogenesis of experimental alcoholism using rats with different levels of alcoholic motivation is discussed.