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Query: KEGG:D06542 (Ethanol)
 9,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.
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PMID:Interaction of biogenic amines with ethanol. 23 68

The purpose of this study was to test the hypothesis that pretreatment with Ca2+ channel blockers would antagonize the effects of ethanol intoxication in humans. The Ca2+ channel blockers verapamil and nifedipine were chosen because preclinical research has shown them to decrease certain behavioral effects of ethanol in animals. Sixteen healthy, male, paid volunteers, moderate users of ethanol, participated in the study (six in the verapamil and 10 in the nifedipine paradigms). Gelatin capsules containing verapamil (80 mg, 160 mg, or placebo) were administered orally 90 min before ethanol ingestion; whereas, gelatin capsules containing nifedipine (10 mg, 20 mg, or placebo) were administered 30 min before ethanol ingestion. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Subjects were tested in a single-blind, latin-square, cross-over design with each of the following six conditions: placebo ethanol-placebo blocker, placebo ethanol-low dose blocker, placebo ethanol-high dose blocker, ethanol-placebo blocker, ethanol-low dose blocker, and ethanol-high dose blocker. The variables measured in this study were subjective rating of ethanol intoxication, Addiction Research Center Inventory alcohol scale, heart rate, blood pressure, short-term memory, accuracy and latency of response in the Simulator Evaluation of Drug Impairment task, and blood ethanol concentrations by breath analyzer. Results indicate that pretreatment with either verapamil or nifedipine failed to antagonize the inebriating effects of ethanol including its decremental effects on short-term memory and psychomotor performance.
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PMID:Interaction between ethanol and calcium channel blockers in humans. 153 Jan 41

Ethanol causes behavioral effects in rats and mice similar to those observed in humans. Moreover, by selective breeding, lines of rats or mice have been obtained that prefer ethanol solution to water and vice versa (ethanol-preferring and ethanol-avoiding animals). Recent studies suggest that ethanol stimulates GABA receptor-mediated opening of the chloride channels in neuronal membranes, and that some behavioral responses to ethanol, such as its sedative and anxiolytic effects, are mediated by central GABA receptors. Recently, we have shown that ethanol suppresses the firing of neurons in the pars reticulata of the substantia nigra, which exert an inhibitory control over dopaminergic neurons. Escaping from inhibitory control, the latter neurons are stimulated by ethanol. Dopaminergic neurons especially sensitive to ethanol are those of the meso-cortico-limbic system, belonging to the "pleasure centers" of the brain. In addiction, it has been shown that ethanol stimulates dopamine metabolism in different brain areas, but more effectively so in ethanol-preferring than in ethanol-avoiding rats. Finally, voluntary ethanol intake modifies dopamine metabolism in different brain areas.
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PMID:[Experimental models of alcoholism]. 216 90

Three patients had neurologic signs due to isopropyl alcohol (IPA) intoxication. Over a several-week period, a known alcoholic developed apathy, confusion, ataxia, and hyperreflexia. During this period, there was no ethanol available to him, and he denied use of other intoxicants. He was found stuporous in the hospital after drinking IPA and admitted to IPA abuse during the preceding weeks. Two other men were admitted in a stupor after large ingestions of IPA. Intoxication with IPA has two different presentations: stupor in a known alcoholic and encephalopathy of unknown cause in individuals who hide their addiction. Ethanol, methanol, IPA, and ethylene glycol intoxications are associated with different clinical and laboratory findings.
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PMID:Isopropyl alcohol intoxication. 198 19

In commenting on the discovery of "opiate" receptors, Goldstein (1976) said: "It seemed unlikely, a priori, that such highly stereospecific receptors should have been developed by nature to interact with alkaloids from the opium poppy" (p. 1081). Endogenous opioid peptides and opioid receptor systems have now been identified in invertebrates that are unlikely to have had ancestors exposed to opium poppies (Kavaliers et al., 1983; Kream et al., 1980; Leung and Stefano, 1984; Stefano et al., 1980). Moreover, endogenous opioids play a role in stress-induced feeding in the slug (Kavaliers and Hirst, 1986) just as they play a role in stress-induced feeding in rodents (Lowy et al., 1980; Morley and Levine, 1980). If we are to understand the actions of opiates and other drugs of abuse we must understand them in terms of their abilities to interact with neural systems that evolved in the service of primitive biological functions, long before any serious incidence of addiction itself. The most primitive axes of the biological substrates of behavior are the axes of approach and withdrawal. Addictive drugs appear to be able to activate the mechanisms of approach, which is termed "positive reinforcement" and to inhibit the mechanisms of withdrawal, which is termed "negative reinforcement." Anatomically distinct sets of pathways have evolved to serve these two forms of reward. Activation of the medial forebrain bundle and associated structures serves positive reinforcement and induces forward locomotion. Approach and forward locomotion are the unconditioned responses to positive reinforcing stimuli such as food and sex partners, and approach to environmental objects and positive reinforcement is induced by electrical stimulation of this structure. The locomotor stimulating effects and the positive reinforcing effects of opiates and psychomotor stimulants result from their activation of this mechanism; stimulants activate the mechanism at the level of dopaminergic synapses of the nucleus accumbens, frontal cortex, and perhaps other forebrain structures, while opiates activate the system at two points: at the level of the dopaminergic synapse and at the level of the afferents to the dopaminergic cell bodies. Ethanol, nicotine, caffeine and phencyclidine stimulate both locomotor activity and dopamine turnover, but their sites of interaction with reward pathways have not yet been identified. Benzodiazepines and barbiturates stimulate locomotor activity without stimulating dopamine turnover; they may interact with reward pathways at a synapse efferent to the dopaminergic link in the pathways.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of reward pathways in the development of drug dependence. 332 Nov 1

The effects of oral pentobarbital on cigarette smoking and subjective response were determined in five adult men with histories of alcoholism and cigarette-smoking habits. Subjects resided in a residential research unit for the 6-wk study and were individually tested 5 days a wk in rooms that were equipped for automatic monitoring of cigarette-smoking behavior. Each subject was tested with placebo, one dose level of ethanol (either 89 or 134 gm absolute ethanol), and each of three pentobarbital doses (200 to 900 mg), in at least four randomized block sequences. Ethanol induced increases in puffs and other smoking measures in all subjects. Pentobarbital increased smoking in two subjects, whereas it did not induce change or suppress smoking in the other subjects. Both pentobarbital and ethanol increased scores on scales of the Addiction Research Center Inventory and other self-report measures. The results indicate that the effects of pentobarbital on smoking differ from those of ethanol, and that the effects of both drugs on smoking may depend on previous experience of the subject in the use of those drugs.
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PMID:Cigarette smoking and subjective response in alcoholics: effects of pentobarbital. 685 12

Effects of oral ethanol, secobarbital and chlorpromazine on human vocalization were studied in a dyadic social situation using repeated observations within subject pairs. Throat microphones and voice operated relays were used to measure quantitative aspects of vocalization (conversational speech) during daily experimental sessions. Ethanol (1-6 oz of 95-proof) and secobarbital (30-300 mg) produced dose-related increases in vocalization by the subject who received active drug, while vocalization by the partner who received placebo only was not generally altered systematically. Chlorpromazine (25-100 mg) produced dose-related decreases in amount of vocalization by the subject and vocalization by partners tended to decrease as well on days when the subject received active drug. Selected scales from the Addiction Research Center Inventory were administered following social sessions to assess subjective drug effects. No consistent changes on ARCI scales were obtained after ethanol or secobarbital, while chlorpromazine produced dose-related increases on the PCAG scale. Overall, quantitative measures of vocalization in a social context provided a reliable and sensitive indicator of dose-related drug effects.
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PMID:Human social conversation: effects of ethanol, secobarbital and chlorpromazine. 723 61

Moderate ethanol consumption reduces stress and increases feelings of happiness and well-being, and may reduce the risk of coronary heart disease. Heavy consumption of alcohol, however, may cause addiction and increases all types of injury and trauma. Environmental and genetic factors are involved in susceptibility to alcoholism. Ethanol can lead to malnutrition, and can exert a direct toxicological effect due to its interference with hepatic metabolism and immunological functions. A causal effect has been observed between alcohol and various cancers. Cessation of alcohol consumption and balanced nutrition are recommended primary nonspecific therapeutic measures for alcoholics. Drug therapies for alcoholics suffering from liver injury has resulted in mixed results. In end-stage liver disease, liver transplantation may be considered.
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PMID:Toxicological effects of ethanol on human health. 757 56

Ethanol-induced locomotor stimulation has been proposed to be positively correlated with the rewarding effects of ethanol (Wise and Bozarth 1987). The present experiments provided a test of this hypothesis using a genetic model. Three behavioral indices of the motivational effects of ethanol (drinking, taste conditioning, place conditioning) were examined in mice from two independent FAST lines, selectively bred for sensitivity to ethanol-induced locomotor stimulation, and mice from two independent SLOW lines, selectively bred for insensitivity to ethanol-induced locomotor stimulation. In a single-bottle procedure, mice were allowed access to drinking tubes containing ethanol in a concentration (1-12% v/v) that increased over 24 consecutive days. FAST mice consumed greater amounts of ethanol solution. In a two-bottle procedure, mice were allowed access to tubes containing water or various concentrations of ethanol (2-8% v/v) over 6 days. FAST mice generally showed greater preference for ethanol solutions than SLOW mice. In a conditioned taste aversion procedure, mice received access to saccharin solution followed by injection of 2.5 g/kg ethanol (IP). SLOW mice developed aversion to the saccharin flavor more readily than FAST mice. In a series of place conditioning experiments, tactile stimuli were paired with various doses of ethanol (0.8-2.0 g/kg). During conditioning, FAST mice showed locomotor stimulation after 1.0, 1.2 and 2.0 g/kg ethanol while SLOW mice did not. During testing, mice conditioned with 1.2 g/kg and 2.0 g/kg ethanol showed conditioned place preference, but there were no line differences in magnitude of preference. These results indicate that genetic selection for sensitivity to ethanol-stimulated activity has resulted in genetic differences in ethanol drinking and ethanol-induced conditioned taste aversion but not ethanol-induced conditioned place preference. Overall, these data provide mixed support for the psychomotor stimulant theory of addiction.
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PMID:Motivational properties of ethanol in mice selectively bred for ethanol-induced locomotor differences. 786 50

In this report a novel animal model of spontaneous development of alcohol and drug addiction was used. Addiction to ethanol was induced in male Wistar rats (free choice between ethanol solutions and water for 11 mo). After 36 wk of alcohol deprivation these rats (series A) had ingested 3.4 +/- 0.4 g ethanol/kg/day. Age-matched, "controlled" alcohol consumers (series C: free choice for 8 wk) had ingested only 1.6 +/- 0.4 g/kg/day (P < .001). Two additional series of addicted (AL) and controlled alcohol-consuming rats (CL) received lisuride (90 micrograms/kg/day) for 8 wk concomitantly with the self-administered ethanol and again during the last week before death. Ethanol intake was increased by lisuride treatment in both groups (AL: 4.1 +/- 0.3 g/kg/day; CL: 2.7 +/- 0.4 g/kg/day; P < .05). Four months before death the alcohol was withdrawn. After this period of abstinence the in vitro dose-response curves for striatal dopamine D-1 receptor-stimulated adenylyl cyclase activity were determined (with eight concentrations of dopamine between 50 nM and 30 microM). Both lisuride-treated (AL) and untreated ethanol-addicted rats (A) displayed a significant (P < .01) increase in the effective concentration required to induce 50% of the response (EC50) as compared with controlled drinkers (C: 720 +/- 150 nM; A: 1820 +/- 390 nM; CL: 590 +/- 110 nM; AL: 1050 +/- 160 nM). Lisuride treatment increased forskolin- (10 microM) stimulated adenylyl cyclase activity and the Bmax of high-affinity [3H]DA binding to the D-1 site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Striatal dopamine receptors and adenylyl cyclase activity in a rat model of alcohol addiction: effects of ethanol and lisuride treatment. 853 Oct 81


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