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Mechanism of alcohol sensitivity and disulfiram-ethanol reaction. 乙醇敏感性及双硫仑-乙醇反应机理。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
S Harada, D P Agarwal, H W Goedde
{"title":"Mechanism of alcohol sensitivity and disulfiram-ethanol reaction.","authors":"S Harada,&nbsp;D P Agarwal,&nbsp;H W Goedde","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human aldehyde dehydrogenase (ALDH) consists of two main isozymes with low and high Km for aldehyde. ALDH isozymes in hair sheats were tested from 40 Japanese using isoelectric focusing and blood acetaldehyde determination with gas chromatography. About 43% of Japanese, who lacked the low Km enzyme (ALDH I) showed an elevated acetaldehyde concentration due to their inability to metabolize acetaldehyde quickly and effectively. Studies regarding the inhibitory reaction of disulfiram and its metabolites have been performed. Among the metabolites, diethylamine inhibited the low Km enzyme strongly. It is presumed that vasomotor symptoms and high acetaldehyde concentration in blood after alcohol intake in patients who are treated with disulfiram might be mainly due to a decrease in activity of the low Km enzyme caused by diethylamine which is produced in vivo as one of the metabolites from disulfiram, rather than to an inhibitory reaction of disulfiram only. Thus, alcohol sensitivity in Mongoloids and disulfiram-ethanol reaction may have a common mechanism.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18151130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ethanol induces a transient susceptibility to audiogenic seizures in weanling C57BL/6J mice. 乙醇诱导断奶C57BL/6J小鼠对听源性癫痫发作的短暂易感性。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
R A Schreiber
{"title":"Ethanol induces a transient susceptibility to audiogenic seizures in weanling C57BL/6J mice.","authors":"R A Schreiber","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An acute dose of 5 g/kg ethanol led to a transient few days of a low incidence of susceptibility to audiogenic seizures in C57BL/6J mice (normally not susceptible) if the ethanol was administered during the transition from suckling to dietary self-sufficiency. This demonstrates a critical period of responsiveness to ethanol, shows ethanol-induced audiogenic priming, and may provide evidence for an indirect effect of ethanol on the brain.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18185567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Indomethacin significantly reduces mortality due to acute ethanol overexposure. 吲哚美辛显著降低急性乙醇过度暴露引起的死亡率。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
F R George, G I Elmer, A C Collins
{"title":"Indomethacin significantly reduces mortality due to acute ethanol overexposure.","authors":"F R George,&nbsp;G I Elmer,&nbsp;A C Collins","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Previous studies in our laboratory have demonstrated that indomethacin, a potent prostaglandin synthetase inhibitor, significantly antagonizes the depressant, activating, and hypothermic responses to ethanol. In this study, male SS mice, a line selectively bred for low sensitivity to the hypnotic effects of ethanol, were pretreated with indomethacin or vehicle up to 24 hr prior to administration of an LD69 dose of ethanol. Indomethacin pretreatment significantly reduced the mortality rate independent of pretreatment time and produced an increase in the number of animals exhibiting a depressed behavioral response as measured by loss of the righting reflex. These results suggest that indomethacin antagonized the effects of ethanol to an extent such that a lethal dose was transformed into a depressant dose. These data are consistent with our hypothesis that pretreatment with prostaglandin synthetase inhibitors serves to shift the ethanol dose response curve to the right, suggesting that the arachidonic acid cascade is an important system in the mechanism of ethanol's actions.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17942164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of two and three compartment models of phencyclidine in man. 苯环利定在人体内二室和三室模型的比较。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
S E Domino, L E Domino, E F Domino
{"title":"Comparison of two and three compartment models of phencyclidine in man.","authors":"S E Domino,&nbsp;L E Domino,&nbsp;E F Domino","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A pharmacokinetic analysis comparing a 2 and 3 compartment model was performed on the published data of Wall et al. (12) on the kinetics of phencyclidine (PCP). These investigators gave 100 micrograms (mean 1.3 micrograms/kg) of 3H-PCP i.v. to three human volunteers and followed the plasma disappearance of PCP over 72 hr. They suggested that PCP followed a 2 compartment model with a plasma half life of 7-16 hr. In the present analysis, additional pharmacokinetic estimations from the plasma data were made and a 3 compartment model developed. The results obtained suggest complex PCP kinetics involving an initial pi half life of 5.5 min, an alpha half life of 4.6 hr, and a beta half life of 22 hr. The volume of distribution was large, varying from 2.2 to 2.4 1/kg for each compartment, suggesting binding of PCP.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18180803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Free amino acids in the brain of ethanol treated rats. 乙醇处理大鼠大脑中的游离氨基酸。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
M Ledig, J R M'Paria, P Mandel
{"title":"Free amino acids in the brain of ethanol treated rats.","authors":"M Ledig,&nbsp;J R M'Paria,&nbsp;P Mandel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Both acute and chronic ethanol administration to rats produce changes in free amino acids involved in nervous system function. Glutamic and aspartic acid levels are especially increased. Chronic ethanol treatment produces in addition an increase in GABA and a decrease in glutamine level. Taurine and glycine were not affected by ethanol. These variations may be explained by changes in transport phenomena and in the redox balance. They seem to correlate with the behavioural effects of acute and chronic alcohol intoxication. Tyrosine, phenylalanine and tryptophan which are related to serotonin and catecholamines formation, were found to be decreased by acute and short chronic ethanol administration.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18151132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Changes in erythrocyte ghost protein phosphorylation associated with physical dependence upon ethanol. 红细胞鬼影蛋白磷酸化的变化与对乙醇的生理依赖有关。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
H C Pant, M Virmani, E Majchrowicz
{"title":"Changes in erythrocyte ghost protein phosphorylation associated with physical dependence upon ethanol.","authors":"H C Pant,&nbsp;M Virmani,&nbsp;E Majchrowicz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of ethanol on phosphorylation in the erythrocyte ghost membranes was studied. Four groups of rats were used: controls; prodromal phase; overt withdrawal syndrome; and treated with a single dose (6g/kg) of ethanol. Spectrin (Band 2) phosphorylation was enhanced during prodromal phase (200 +/- 12%) and during overt ethanol withdrawal syndrome (150 +/- 18%), while a single dose of ethanol produced no significant change. Addition of micromolar calcium chloride solution to the phosphorylating medium produced pronounced decrease in spectrin phosphorylation in the ghost membranes isolated from controls and those treated with a single dose of ethanol, while this effect of calcium was less pronounced in the ghost membranes isolated from rats in the prodromal phase and in the withdrawal syndrome. This suggests that due to prolonged ethanol treatment membrane phosphorylating properties were less sensitive to the change in calcium concentration. The membrane polypeptide composition was unaffected upon ethanol treatment.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17942062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Concerning the decarboxylation of 3-carboxysalsolinol. 关于3-羧基茴香醇的脱羧。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
A M Marshall, M Hirst
{"title":"Concerning the decarboxylation of 3-carboxysalsolinol.","authors":"A M Marshall,&nbsp;M Hirst","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>3-Carboxysalsolinol (14C-COOH) was prepared from DOPA (1-14C). Both in vitro and in vivo studies were conducted to examine the possibility that this amino-acid tetrahydroisoquinoline is converted to salsolinol in a parallel manner to the formation of dopamine from its amino-acid precursor. The results showed that this is not so for DOPA is decarboxylated far more readily than is 3-carboxysalsolinol. Small quantities of carbon dioxide (14C) are liberated from 3-carboxysalsolinol (14C-COOH), but this may reflect non-enzymatic decarboxylation.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17870882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Palatability-induced drinking after administration of morphine, naltrexone and diazepam in the non-deprived rat. 给予吗啡、纳曲酮和地西泮后大鼠适口性饮酒。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
S J Cooper
{"title":"Palatability-induced drinking after administration of morphine, naltrexone and diazepam in the non-deprived rat.","authors":"S J Cooper","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Rats consumed excessive quantities of a highly palatable 0.005M sodium saccharin solution in the absence of depletion of body fluid compartments. The taste strongly promoted drinking, and the consequent fluid consumption proved to be very sensitive to opiate receptor blockade. Naltrexone, at a dose as small as 0.03 mg/kg, significantly attenuated consumption of the saccharin solution in the first hour of access. The naltrexone treatment did not affect latency to drink, and its suppressant effect was transient, indicating that it did not induce either immediate or lasting avoidance of the saccharin solution. The naltrexone-induced suppression was also not due to elicited stress or anxiety, since concurrent administration of diazepam did not reverse the naltrexone effect. Morphine (0.3-3.0 mg/kg) failed to enhance saccharin solution intake over a 6 hr test period. Morphine (10 mg/kg) produced immobility and an extended suppression of drinking, which was followed by a secondary hyperdipsic response.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18180804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alcohol and pregnancy: a clinical perspective for laboratory research. 酒精与妊娠:实验室研究的临床视角。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
R J Sokol
{"title":"Alcohol and pregnancy: a clinical perspective for laboratory research.","authors":"R J Sokol","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Based on clinical experience, review of the literature and clinical research results, four areas, in which laboratory investigations might contribute significantly to better understanding of the effects of alcohol on pregnancy outcome, are suggested for consideration--1) mechanisms, 2) timing, pattern and source of fetal alcohol exposure, 3) dose/response and threshold, and 4) susceptibility. By focusing on issues of current clinical impact, the laboratory scientist may contribute to improved pregnancy outcome in humans.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18184148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Responding under a fixed interval schedule of intravenous ethanol presentation in the rat. 在大鼠静脉注射乙醇的固定间隔时间表下有反应。
Substance and alcohol actions/misuse Pub Date : 1982-01-01
L A Grupp, E Perlanski
{"title":"Responding under a fixed interval schedule of intravenous ethanol presentation in the rat.","authors":"L A Grupp,&nbsp;E Perlanski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Specific behavioural procedures have been developed which lead animals to give themselves electric shock. The present study investigated the possibility that the same set of procedures would lead to intravenous (i.v.) ethanol self-administration. Three rats were trained to press a bar under a concurrent schedule which delivered food pellets on a variable interval (VI) 60 sec or 120 sec schedule and ethanol infusions on a fixed interval (FI) 600 sec schedule. A fourth animal was trained under the same concurrent schedule with vehicle rather than ethanol infusions. When the food schedule was subsequently omitted (extinction) and only ethanol was presented for responding, bar pressing rapidly extinguished. In one animal tested with a very high dose of ethanol, drug-elicited bar pressing indicative of an aversive reaction to the drug was observed. Although similar procedures are sufficient to engender response-produced shock presentation they were not successful in fostering i.v. ethanol self-administration and by implication, in establishing ethanol as a positive reinforcer.</p>","PeriodicalId":22076,"journal":{"name":"Substance and alcohol actions/misuse","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18198580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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