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

The inhibition of glycolysis during ethanol oxidation has been examined in isolated hepatocytes from fasted rats. Glycolytic flux was measured by determining the rate of release of tritium from [6-3H]glucose. During ethanol oxidation, the rate of glycolysis was inhibited 80% in freshly prepared hepatocytes, in which shuttle intermediates are depleted, but was depressed only about 20% in the presence of asparagine, a condition under which activity of the malate/aspartate shuttle was restored to normal levels. The inhibition of glycolysis was also partially released by addition of pyruvate and when alcohol dehydrogenase activity was depressed by 4-methylpyrazole. Titrations with this inhibitor revealed inverse linear relationships between the rates of glycolysis and ethanol oxidation. For any given rate of ethanol oxidation, glycolytic flux was lowest and the [lactate]/[pyruvate] ratio highest in the presence of aminooxyacetate, an inhibitor of the malate/aspartate shuttle, whereas flux was highest and the ratio lowest in the presence of asparagine. During these titrations with 4-methylpyrazole the inhibition of ethanol oxidation and concomitant restoration of glycolysis were accompanied by a decline in the [lactate]/[pyruvate] ratio, a substantial fall in the rate of reducing-equivalent transfer from cytoplasm to mitochondria and an increase in lactate accumulation. These findings imply that the reducing equivalents generated during ethanol oxidation compete with those arising in glycolysis for transfer to the mitochondria. This competition leads to an inhibition of aerobic glycolysis, and at the same time contributes to a rise in cytoplasmic NADH and fall in NAD+ that results in depression of anaerobic glycolysis. Allosteric inhibition of 6-phosphofructo-1-kinase due to a decrease in the concentration of fructose 2,6-bisphosphate did not appear to play a primary role in the inhibition of glycolysis by ethanol. Ethanol oxidation had no effect on glucose phosphorylation as measured with [2-3H]glucose, but induced a substantial increase in cycling between glucose and glucose 6-phosphate.
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PMID:The capacity of reducing-equivalent shuttles limits glycolysis during ethanol oxidation. 795 70

Hormones level and lipid peroxidation processes under influence of acute alcohol intoxication are tested in testes and adrenals of rats. Ethanol marker effects--the rise of corticosterone biosynthesis and depression of testosterone concentration--were reproduced in the experiment. At the moment of maximal changes in steroid levels indices characterising lipid peroxidation didn't differ from the control. At the early stage of the experiment transient shifts in malonic dialdehyde and dienic conjugates levels were noted. The data obtained does not agree with the hypothesis of acute ethanol effects in testes and adrenals being mediated through the changes of lipid peroxidation rate.
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PMID:[Effect of acute alcohol intoxication on lipid peroxidation in testis and adrenal glands of rats]. 797 6

The relationship between subjective effects and drug preferences in normal volunteers was explored in a meta-analysis of several previously published studies. Subjective effects of, and preference for, ethanol and diazepam vs. placebo were measured using a choice procedure. Subjects were grouped according to their drug choices: 'non-choosers' never chose drug, whereas 'choosers' always chose drug. The two groups were compared on their subjective responses to drug and on demographic variables. Ethanol decreased Arousal, Elation, Positive Mood and Vigor, and increased Anxiety, Depression and Fatigue in the non-choosers, whereas it increased Arousal and Vigor in the choosers. Ethanol choosers were also more likely to be males and/or full-time students than non-choosers. Diazepam produced sedative-like effects in both choosers and non-choosers, but markedly decreased Anxiety and increased Friendliness in choosers only. Diazepam choice was also associated with more frequent recreational use of marijuana and stimulants. Thus, both demographic variables and subjective drug effects were related to drug preference.
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PMID:Relationship between subjective effects and drug preferences: ethanol and diazepam. 803 63

The uptake of 2-deoxy-D-[14C]glucose (2-DG) has been used with some success to identify neuronal sites of drug action, and has also been useful in identifying brain regions that are differentially sensitive to ethanol in selectively bred rat lines, the alcohol tolerant (AT) and alcohol nontolerant (ANT) lines. The studies reported here utilized the 2-DG method in an attempt to ascertain whether the LS and SS mouse lines, which were selectively bred for differences in sensitivity to high dose, anesthetic effects of ethanol, do so because of disruption of specific neuronal sites. LS and SS mice were injected with saline or a 4.0-g/kg dose of ethanol 15 min before injection with 2-deoxy-D-[14C]glucose, and uptakes into blood, eight brain regions, the liver, and adrenal tissues were measured 2-60 min afterwards. Ethanol produced statistically significant decreases in 2-DG uptake into every region of the LS mouse brain, but only three brain regions showed significant decreases in uptake in the SS brain. Other SS brain regions showed a trend towards decreased uptake, but these trends were not significant. A comparison of percent decrease in 2-DG uptake across all brain regions showed that ethanol decreased 2-DG uptake approximately twice as much in LS brain regions as in SS brain regions. Since 2-DG uptake into adrenal and hepatic tissue was not affected by ethanol injection in either mouse line, it seems likely that the decreased 2-DG uptake, seen more readily in the LS brain, is due to ethanol-induced central nervous system (CNS) depression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol effects on 2-deoxyglucose uptake into tissues obtained from LS and SS mice. 812 11

Few studies have investigated genetic differences in the effects of ethanol on operant schedule-controlled behaviors. The use of genetically defined populations in sensitive measures of complex behavior can help determine genetically covarying responses to ethanol as well as environmental contexts important for demonstrating genetic differences. The purpose of the present study was to investigate the rate depressant effects of ethanol on two lines of mice selectively bred for increased, LS/Ibg (LS), and decreased, SS/Ibg (SS), sensitivity to the acute narcotic effects of ethanol. Ethanol dose-dependently decreased high rates of behavior maintained by fixed ratio responding for water in both the LS and SS mice. Interestingly, the LS and SS mice did not differ in the rate depressant effects of ethanol under these conditions despite the sensitivity of this measure to the CNS effects of drugs and the very large differences between these lines in sensitivity to numerous other ethanol-related effects. While the SS mice were slightly less sensitive, and LS mice tended to show a low dose rate increasing effect, none of the differences were significant as ED50 values for rate depression differed by only 2.5 percent. The results of this experiment demonstrate that sensitivity to the effects of ethanol on fixed ratio responding for water is not genetically related to the acute narcotic effects of ethanol. In addition, the findings show that previously reported differences in operant ethanol self-administration between these two lines of mice are not due to differential sensitivity to the direct effects of ethanol on reinforced behavior.
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PMID:Operant rate depressant effects of ethanol in mice selectively bred for differential neurosensitivity to ethanol. 820 79

This study characterized the antagonistic effects of hyperbaric exposure on the dose-response curve for ethanol-induced depression of locomotor activity. Drug-naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0, 2.5, or 3.0 g/kg ethanol, and were exposed to 1 atmosphere absolute (ATA) air or 12 ATA helium-oxygen gas mixtures (heliox) at temperatures that offset the hypothermic effects of ethanol and helium. Locomotor activity was measured 10-30 min after injection. In addition, the effects of exposure to 12 ATA heliox on blood ethanol concentrations were tested in a separate group of mice injected with 2.5 g/kg ethanol. Ethanol produced a dose-dependent depression of locomotor activity beginning at 2.0 g/kg. Exposure to 12 ATA heliox completely antagonized the locomotor depressant effects of 2.0 and 2.5 g/kg ethanol and partially blocked the effects of 3.0 g/kg. Activity in mice given 1.5 g/kg ethanol was not significantly affected at 1 ATA air, but was significantly increased at 12 ATA heliox. Low-level hyperbaric exposure shifted the ethanol dose-response curve to the right with a resultant increase in the ED50 of ethanol for locomotor depression from 2.6 to 3.3 g/kg. Exposure to 12 ATA heliox did not alter blood ethanol concentrations in mice injected with 2.5 g/kg ethanol. These findings with 12 ATA heliox present key new evidence for the hypothesis that low-level hyperbaric exposure acts directly, with a pattern analogous to a competitive, mechanistic antagonist of ethanol.
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PMID:Low-level hyperbaric antagonism of ethanol-induced locomotor depression in C57BL/6J mice: dose response. 827 77

The effects of chronic embryonic ethanol exposure were evaluated in chick ventricular muscle. Ethanol treatments were administered on embryonic days 11, 13, 15, and 17 and chicks were sacrificed at various time points following treatments. Fluctuations in embryonic blood ethanol levels were examined following treatments. Developmental increases in the activities of mitochondrial enzymes, cytochrome oxidase (CO) and citrate synthase (CS), were observed. Ethanol exposure resulted in a depression in CO activity, but not CS activity. Since, a maximal depression in CO activity was seen with ethanol treatments of 75 mg/100 g, this dosing paradigm was adopted for subsequent experiments. A tissue-specific effect of ethanol was demonstrated as CO activity was unchanged in atrial, liver, pectoralis, and brain tissues. The role of mitochondrial DNA replication and transcription during the developmental up-regulation and ethanol-induced down-regulation of CO activity was evaluated using a cDNA probe for cytochrome oxidase subunit III (COIII). The relative levels of COIII mRNA and mitochondrial DNA (cpm/mg protein) decreased by 3-fold and 4-fold, respectively, across the developmental time course, while CO activity increased by 3.5-fold. Therefore, increases in mitochondrial DNA and mitochondrial mRNA transcripts are unlikely to be responsible for the developmentally-regulated increases in CO activity. Similarly, embryonic ethanol exposure failed to elicit alterations in COIII mRNA levels, indicating that the ethanol-induced depression in CO activity was not transcriptionally regulated. However, ventricular mitochondrial DNA concentrations were elevated in ethanol-treated embryos, indicating that ethanol-exposure either directly or indirectly induces mitochondrial DNA replication.
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PMID:Ventricular mitochondrial gene expression during development and following embryonic ethanol exposure. 838 53

Acute ethanol's influence on field L auditory-evoked potentials (AEP) was studied in 4-7-days-old altricial nestlings of the pied flycatcher. Nestlings were presented with behaviorally meaningful tone pips (2.0 and 5.0 kHz) and control tone pips (3.0 kHz). Ethanol ingestion was found to reduce the N1 amplitude and maturity index (MI) of the AEP in response to "behavioral" but not to control frequencies. This effect was first observed on day 5, when the nestlings' behavior became more complex (their eyes opened and defence behavior appeared), and when previously formed feeding behavior was undergoing modifications. The MI increase during the early postembryonic ontogeny was probably due to the selective involvement of neurons with newly formed behavioral specializations into the subserving of new behavioral patterns, while the decrease of the MI under alcohol was due to the depression of activity in these neurons.
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PMID:Changes of auditory-evoked potentials in response to behaviorally meaningful tones induced by acute ethanol intake in altricial nestlings at the stage of formation of natural behavior. 850 90

The postnatal development of certain neurochemical correlates of CNS ethanol sensitivity was examined in the long-sleep (LS) and short-sleep (SS) mice. The differences in sensitivity to the motor-incoordinating and hypothermic effects of ethanol emerged during the second and third weeks of life. Prior studies have shown the sleep time differences between LS and SS mice became significant at 8-10 days of age whereas the present results established that the differences in ethanol-induced hypothermia became prominent at 12-16 days of age. Previous results from our laboratory suggested that the greater CNS ethanol behavioral sensitivity (sleep time and hypothermia) of LS mice is related to the greater ethanol-induced depression of brain monoamine synthesis in the LS line. The timing of the developmental changes in neurochemical ethanol sensitivity in LS and SS mice was found to parallel that found in the development of behavioral ethanol sensitivity as follows. Ethanol-induced decreases in in vivo tyrosine hydroxylase activity in the cerebellum, hypothalamus, and brain stem did not differ between LS and SS mice at postnatal day 8, but became substantially greater in LS mice between postnatal days 8 and 12, coincident with the appearance of the greater sleep times of LS mice. Likewise, ethanol-induced decreases in in vivo tryptophan hydroxylase activity in the dorsal raphe and hypothalamus, which were similar in LS and SS mice at postnatal days 8 and 12, became significantly greater in LS mice by postnatal day 16, the age at which their increased sensitivity to ethanol-induced hypothermia appeared.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice. 851 37

The heart is a major locus for the toxic actions of cocaine and ethanol, each of which has been shown to interfere with excitation-contraction coupling in cardiac muscle cells. Because these drugs are frequently used in combination, the present study was designed to investigate how they interact to modify the Ca2+ transient and associated contraction in fura2-loaded cardiomyocytes. A high-speed imaging technique using a charge-coupled device as detector and short-term image store was used to measure cytosolic Ca2+ and contraction simultaneously from fluorescence images obtained during the contractile cycle. Ethanol (100 mM) and cocaine (50 microM) caused reversible reductions in Ca2+ transient amplitude of 24.3 +/- 3.0% and 25.1 +/- 3.6%, respectively. Neither agent modified basal Ca2+. Ethanol treatment decreased peak shortening by 44.3 +/- 3.5%, whereas the contractile depression by cocaine was 31.4 +/- 5.3%. The relatively greater effect of ethanol on contraction resulted from a Ca2+-independent component of ethanol action on contractility. When cardiomyocytes were exposed simultaneously to ethanol and cocaine, Ca2+ transient amplitude was reduced by 38.7 +/- 3.0%, and peak contraction was decreased by 55.1 +/- 3.5%. These values represent a significantly greater inhibition than observed with either drug alone (p < 0.02) and are compatible with additive effects of the two drugs acting at distinct loci within the excitation-contraction coupling pathway. Thus, simultaneous use of cocaine and ethanol leads to an enhanced depression of myocardial contractility, which is likely to contribute to the cardiotoxic actions of the combination of these two drugs.
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PMID:Ethanol and cocaine cause additive inhibitory effects on the calcium transients and contraction in single cardiomyocytes. 889 30


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