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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The direct effects of ethanol on cardiac contractility are controversial, probably because of methodological reasons in relation to the choice of appropriate experimental models. We studied the direct effects of 1, 2, 5 and 10 g/l ethanol on myocardial performance and metabolism in the isolated perfused working guinea-pig heart. In the normal heart ethanol induced a dose-dependent, fully reversible depression of cardiac contractility without significant changes of heart rate or cardiac metabolism. In the post-anoxic failing heart this effect was more pronounced. Ethanol had no arrhythmogenic effect even at high concentrations. Finally, it had no measurable effect on anoxic-induced alterations or post-anoxic recovery after a period of 20 minutes of anoxic perfusion. However anoxic-induced lactate production was decreased in hearts pretreated with 10 g/l ethanol. These results demonstrate the direct negative inotropic effect and the lack of chronotropic effect of ethanol. They suggest the lack of effect on excitability. The mechanism of the negative inotropic effect does not seem to be metabolically related since cardiac oxygen consumption and lactate production remained unaltered.
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PMID:[Acute effects of ethanol on the performance and metabolism of the isolated working heart, both normal and failing]. 390 Aug 85

The effect of different doses of ethanol (0.5, 1.0, 2.0 and 4.0 g/kg) on LH, FSH and prolactin levels has been studied in female rats. Ethanol was administered in preovulatory periods (18 hr of diestrous or 9 hr of proestrous) and hormonal levels were measured at the 18 hr of proestrous. Ethanol administered at the 18 hr of diestrous produces a biphasic effect on serum LH levels. High doses of alcohol significantly decreased LH levels, whereas low doses (0.5 g/kg) increased the hormonal levels. When ethanol-treatment was at the 9 hr of proestrous, it only decreased LH levels with the dose of 4.0 g/kg. Serum FSH levels were unaffected by the preovulatory administration of ethanol. Serum prolactin concentrations were significantly elevated after i.p. administration of ethanol at the 18 hr of diestrous and the 9 hr of proestrous. The hyperprolactinemia is more pronounced in the rats treated at the 9 hr of proestrous. The results of these studies suggest that the ability of ethanol to modify LH and prolactin levels is due to a central depression caused for alcohol. These effects of ethanol could be mediated by the hypothalamic releasing factors and/or could be due to a direct action on the pituitary function. The sum of these effects produces important failures of the reproductive function in the female rat.
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PMID:Further evidence for effects of ethanol on gonadotrophins and prolactin secretion in female rats. 392 Jan 18

The acute effects of alcohol on spontaneous locomotor activity in male Swiss mice were studied at various times after an IP injection of 2 g/kg ethanol. Subjects were placed alone in a novel arena and videotape recordings were made of behaviour: trials were of 500-s duration and commenced at either 30, 60, 120, or 180 min after alcohol administration. Measures of behaviour included various indices of ambulation and immobility, together with a more detailed ethological analysis of the frequencies of all other acts and postures shown by test animals. Ambulation showed a biphasic response to alcohol treatment, consisting of an initial stimulation followed by a suppression after 3 h. Immobility was also increased by alcohol, and showed peak stimulation in trials commencing 30 min after administration: thereafter there was a progressive return to baseline levels. Many behavioural elements were suppressed including rearing, digging, shaking, and abbreviated grooming. Ethanol thus appeared to produce two distinct types of depression, in terms of increased immobility (and suppression of other behaviour) and in terms of decreased ambulation, the latter occurring when immobility had returned to baseline levels.
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PMID:Time course of the locomotor stimulant and depressant effects of a single low dose of ethanol in mice. 392 Jun 99

The effect of ethanol upon the oxidation of leucine by the rat in vivo was determined. The rate of leucine oxidation was not significantly altered by chronic administration of ethanol (20% v/v solution as drinking water for 28 days). Ethanol administered acutely (8 g kg 0.73) significantly decreased leucine oxidation by the rat in vivo. This decrease appeared to be independent of a more general depression of oxidation metabolism. Decrease in leucine oxidation by ethanol is discussed in relation to the regulation of tissue leucine pool sizes in vivo.
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PMID:Ethanol and leucine oxidation--I. Leucine oxidation by the rat in vivo. 392 78

In vitro studies have shown that acetaldehyde is a more potent inhibitor of testicular steroidogenesis than ethanol. The present study examined the in vivo role of acetaldehyde in ethanol-induced reduction of testosterone by (1) determining the levels of acetaldehyde to which the testes were exposed subsequent to acute ethanol administration to mice; and (2) examining the effect of ethanol on testosterone in animals subsequent to drug pretreatment which decreased or increased ethanol-derived acetaldehyde. Ethanol-induced (3 g/kg) depression of testosterone was dependent upon gonadotropin stimulation. The increase in hCG-induced testosterone was suppressed (P less than 0.01) in ethanol- as compared to saline-treated animals [39.8 +/- 2.6 (S.E.M.) vs 28.1 +/- 2.3 ng/ml]. Pargyline (100 mg/kg) or cyanamide (8.4 mg/kg) increased (P less than 0.05) plasma and testicular acetaldehyde, while having no effect on the testosterone response to ethanol. Similarly, 4-methylpyrazole (25 mg/kg) reduced blood and testicular acetaldehyde to nondetectable levels, while having no effect on testosterone. Testicular acetaldehyde was lower (P less than 0.001) than plasma levels (14 +/- 2 vs 2.0 +/- 0.2 microM). This functional blood-testis barrier to acetaldehyde could be explained by testicular aldehyde dehydrogenases in the mitochondria (Km for acetaldehyde = 1.5 microM) and in the cytosol (Km = 123 microM) whose maximal activities totaled to more than 25-fold greater than that of testicular alcohol dehydrogenase (ADH). ADH was concentrated in the Leydig cells, while aldehyde dehydrogenase was evenly distributed in the testis. Ethanol prevented further hCG-induced rises in testosterone rather than inhibiting testosterone production to below pre-ethanol values. The above data argue against a significant role of acetaldehyde in the in vivo response of testosterone to ethanol. Ethanol appears to impair gonadotropin-testicular receptor interaction in vivo.
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PMID:Demonstration of a functional blood-testis barrier to acetaldehyde. Evidence for lack of acetaldehyde effect on ethanol-induced depression of testosterone in vivo. 397 44

The effect of variable doses of ethanol on plasma lecithin: cholesterol acyltransferase (LCAT) activity was examined in male, atherosclerosis-susceptible squirrel monkeys over a 12-month period. Primates were divided into three groups: 1) Controls fed isocaloric liquid diet; 2) Low Ethanol monkeys given liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) High Ethanol animals fed diet plus vodka at 24% of calories. There were no significant differences between the treatments in serum glutamate oxaloacetate transaminase (SGOT), a measure of liver function. However, plasma LCAT activity (% esterification/min) measured in vitro was significantly reduced in High Ethanol monkeys while cholesterol esterification was elevated in the Low Ethanol group and intermediate in Controls. Similarly, the in vivo appearance of radiolabeled cholesteryl ester in high density lipoproteins (HDL) following the intravenous injection of 3H mevalonolactone was highest in the Low Ethanol primates, intermediate in Controls and significantly lower in monkeys fed the high alcohol diet. In vitro measurement of LCAT enzyme efficiency was similar for the three groups while substrate efficiency was lower in the High Ethanol treatment. Although LCAT activator (apoprotein A-I) was not markedly altered by dietary ethanol and the concentration of LCAT substrates (HDL free cholesterol and phosphatidyl choline) was significantly elevated in the High Ethanol group, subtle modifications in substrate-product composition may account for the observed reduction in cholesterol esterification. These include potential substrate and/or product LCAT inhibition resulting from increased concentrations of plasma free cholesterol, HDL lysophosphatidyl choline, and higher HDL2/HDL3 subfraction ratios, as well as alterations in HDL phospholipid fatty acid profiles in the High Ethanol group. Results from this study provide the first evidence of an anomalous enhancement in LCAT activity in nonhuman primates fed ethanol at 12% of calories and a marked depression in cholesterol esterification at the 24% dose which may be due to substrate alterations and product inhibition prior to overt biochemical evidence of liver dysfunction.
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PMID:Effect of ethanol on lecithin:cholesterol acyltransferase (LCAT) activity. 399 6

Tolerance to the cardioacceleratory and hypothermic effects of ethanol was studied in unanesthetized, freely-moving rats surgically implanted with EKG electrodes and biotelemetric temperature sensors. Different groups received 0.0, 1,0 or 2.0 g ethanol/kg body weight in injections given every other day for a total of nine injections. Heart rate and body temperature were recorded for 1 hr before and 2 hr after each injection. Ethanol initially induced a monophasic dose-related cardioacceleration (80 bpm) and hypothermia (1.0 degrees C) that persisted throughout the 2-hr sample period. Tolerance developed to the hypothermic, but not to the tachycardic effect of ethanol. Assuming that tolerance depends on level of impairment in specific neuronal pathways, this outcome suggests that these two effects of ethanol are not mediated through a common autonomic mechanism (e.g., vasomotor depression) and/or that tolerance to the hypothermic effect is due to alterations in pathways unique to the thermoregulatory system. Overall, the finding is consistent with those of studies showing development of tolerance to depressant, but not to excitatory drug effects.
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PMID:Dissociation of tolerance to the hypothermic and tachycardic effects of ethanol. 402 29

1. Slices of rat cerebral cortex, incubated anaerobically at 37 degrees , lost K(+) from an initial concentration of 102m-equiv./kg. to a concentration of 57m-equiv./kg. after 10min. On subsequent aerobic incubation they regained K(+) rapidly at a rate that varied with the K(+) concentration of the medium. 2. Lower aliphatic alcohols, present at equal thermodynamic activity, produced approximately equal degrees of inhibition of K(+) uptake during the aerobic incubation. This inhibition was reduced by an increase in K(+) content of the medium. Ethanol did not affect the rate of K(+) loss during anaerobic incubation. 3. Li(+), in concentrations of 1-10mm, also inhibited K(+) uptake by brain-cortex slices, the degree of inhibition varying with the Li(+) concentration. Ouabain also inhibited K(+) uptake. 4. The same series of alcohols, at equal thermodynamic activity, produced comparable degrees of inhibition of Na(+),K(+),Mg(2+)-stimulated adenosine-triphosphatase activity in brain microsomes. 5. It is suggested that inhibition of cation transport is an important, but not a primary, mechanism in the production of central nervous depression by alcohols and other substances.
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PMID:Effects of lower alcohols on potassium transport and microsomal adenosine-triphosphatase activity of rat cerebral cortex. 422 75

To study the possible hepatotoxicity of vitamin A supplementation and its potentiation by ethanol, rats were fed diets with either normal or fivefold increased vitamin A content, both with or without ethanol. Ethanol with a normal vitamin A diet produced the expected proliferation of the smooth endoplasmic reticulum and moderate mitochondrial lesions. Vitamin A supplementation by itself produced endoplasmic reticulum proliferation, slight enlargement of mitochondria, and moderate decrease in cytochrome oxidase activity and cytochrome aa3 content. The combination of high vitamin A and ethanol resulted in much more striking lesions, with giant mitochondria containing paracrystalline inclusions and depression of oxygen consumption in state-3 respiration with five different substrates, including palmitate and palmitoyl coA. The depression of fatty acid oxidation may have contributed to the lipid accumulation. The blood levels of vitamin A were unaffected whereas liver levels of vitamin A were increased by vitamin A supplementation and decreased by ethanol. As a net result the liver vitamin A content of the high-A-ethanol groups was not greater than that of the normal-A-control group, suggesting that a metabolite of vitamin A rather than vitamin A itself may have been responsible for the potentiation of vitamin A toxicity by ethanol. Mitochondrial toxicity reflected itself also in decreased content of various cytochromes and reduced activity of enzymes, including glutamate dehydrogenase. The activity of the latter was increased in the serum. Implications of these findings for the routine treatment of alcoholics with vitamin A and the monitoring for possible signs of toxicity are discussed.
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PMID:Hepatotoxicity of vitamin A and ethanol in the rat. 627 29

The effects of combined administration of ethanol (4 g/kg) and chlordiazepoxide (CDP, 12.5 mg/kg) on mouse brain c-AMP and c-GMP levels were investigated in order to test the hypothesis that the supra-additive effect of CDP on ethanol sleep time may be related to a supra-additive alteration in brain cyclic nucleotide levels induced by the combined drugs. Ethanol alone or CDP by itself did not cause any change in brain c-AMP levels, except for a transient decrease in the cerebral cortex and midbrain at 0.5 hr after ethanol injection, as well as a transient increase in the cerebellum at 0.5 hr after CDP injection. The combined drug treatment did not result in a supra-additive effect on c-AMP levels. On the other hand, c-GMP levels were depressed significantly for 4 hr after ethanol injection especially in the cerebellum. The mice regained the righting reflex when the c-GMP levels were still about 30 per cent of control values. Ethanol and CDP together induced a supra-additive decrease of c-GMP concentrations in the cerebellum at 2 and 4 hr. This resulted in a lengthened period (about 2.5 hr) during which the cerebellar c-GMP levels were below 30 per cent of control values, and this interval coincided with the increase in sleep time, suggesting a possible relationship between these two factors. Injection of ethanol and N-demethyl-chlordiazepoxide (NDCDP) simultaneously (the latter being a metabolite of CDP) also elicited a more than additive depression of cerebellar c-GMP levels at 4 hr. These data suggest that NDCDP or its metabolite could be responsible for the supra-additive effect of CDP on the ethanol-induced decrease in cerebellar c-GMP levels.
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PMID:Relationship of brain cyclic nucleotide levels and the interaction of ethanol with chlordiazepoxide. 627 37


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