Substance and alcohol actions/misuse最新文献

Mice were injected with 0, 107, 215, 430, or 1720 mg/kg of ascorbic acid. Thirty min later they were tested for ethanol (3.5 g/kg) induced sleep time. Brain ethanol levels were determined upon awakening. Another group of mice were tested for apomorphine (3 mg/kg) induced locomotor activity also 30 min after ascorbic acid injection. Ascorbic acid in doses above 215 mg/kg augmented ethanol sleep time up to 210% at the highest doses, the increase being significant from 430 mg/kg. Brain ethanol levels upon awakening were reduced by ascorbic acid treatment; this reduction was significant at 1720 mg/kg dose. Ascorbic acid decreased apomorphine-induced locomotor activity in a dose response manner that paralleled the ascorbic acid increase of ethanol sleep time. At the highest dose of ascorbic acid, apomorphine-induced locomotor activity was completely eliminated. It is suggested that ascorbic acid increases brain sensitivity to ethanol by lowering the activity of dopamine receptors.

Recent evidence indicates that alcohol (ethanol) exerts specific effects on dopaminergic-enkephalinergic neuronal pathways which are involved with natural drive-induction and have also been implicated in reward and memory consolidation. It is proposed herein that the euphorigenic and "paradoxical" memory-enhancing effects of low doses of alcohol are related to its direct actions on this specific brain substrate.

The effect of chronic ethanol consumption on the binding (125I)-iodohydroxybenzylpindolol to beta-adrenergic receptors in rat brain microvessels has been studied. The results show that chronic ethanol treatment increases the number of beta-receptors present in brain microvessels without changing the binding affinity of the binding site for the beta-adrenoceptor ligand. This effect is apparently not associated with changes in peripheral adrenergic tone, since no differences in platelet epinephrine or norepinephrine concentrations were found between ethanol-treated and control animals. An increase in beta-receptor density in brain microvessels might contribute to the alterations of cerebral blood flow and oxygen consumption reported during chronic ethanol intoxication.

Rats treated acutely with ethanol showed a significant increase in biliary bilirubin secretion and in serum bilirubin levels (compared to saline treated controls); no difference was found in bile acid secretion. In rats fed ethanol chronically (36% of total energy for 4-6 weeks) there was a significant increase in the secretion of bilirubin and bile acids when compared to pair fed controls. We observed this effect either in the presence or in the absence of alcohol in the blood at the time of the experiment. The presence of ethanol in the blood, however, resulted in higher biliary and serum bilirubin levels. The increase in bile acid secretion involved selectively di- (but not tri-) hydroxy bile acids. Since increased secretion of unconjugated bilirubin favors pigment gallstones formation, it can be postulated that ethanol contributes to the pathogenesis of cholelithiasis by enhancing the biliary secretion of the pigment.

Alcohol misuse has taken on epidemic proportions among some (but not all) American Indian populations. Cultural, psychological, socioeconomic and genetic etiologies have been offered to explain this social phenomenon. This study identifies the relative strengths of these causal models to differentiate among both current and lifelong drinking career patterns. Further, antecedent and drinking level differences between urban and rural Indian populations in California are described. Age, sex, level of stress as measured by the Cornell Medical Index, percent of Indian ancestry and level of drinking in the family of origin are less powerful predictors of drinking level. Policy implications of these findings include: the development of intervention programs which involve members of the patient's support network, accelerated interventions in rural Indian communities and mid-level interventions among younger and less debilitated, but identifiably "at risk", populations.

Accumulation in the rat striatum of 3,4-dihydroxy-L-phenylalanine (DOPA) after inhibition of the neuronal decarboxylase was not significantly altered in the early abstinence after chronic treatment with barbital for 36-39 weeks in comparison with controls treated with water. Pilocarpine (10 mg/kg i.p.) increased the accumulation of DOPA in rats chronically treated with barbital and also in controls treated with water. Some weak correlations between striatal DOPA accumulation and changes in body weight or fluid consumption during the first three days of the abstinence were observed. There was also a highly significant, positive correlation (r = 0.85) between striatal DOPA accumulation and the number of convulsions in rats chronically treated with barbital and injected with NaCl. The corresponding correlation in rats chronically treated with barbital and injected with pilocarpine was positive but not significant (r = 0.50). No evidence for an increased sensitivity at muscarinic receptors in the striatum was found.

Through means of a daily diary, alcohol consumption patterns of students at a major metropolitan university were studied. Drinking displayed a weekly pattern which reflected student role demands, but was also influenced by family roles, external events, and fluctuations in academic pressures. There were distinct patterns in both percentage of students drinking and in mean ethanol consumption per drinker. There was also a clear pattern of "binge" drinking in the aftermath of stress. Drinking in the campus context was both quantitatively and qualitatively different from drinking in the family context. Chronographic analysis provides a key to understanding behavior which complements cross-sectional or longitudinal panel analysis.

Adult C57/BL mice subjected to short term ethanol liquid diets exhibited significant increases in liver microsomal phosphatidylethanolamine methyltransferase activity(s) as well as changes in microsomal lipid composition. Specifically, increases in [3H]-methyl incorporation into phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine were observed suggesting increases in phospholipid methyltransferase I and the first methyl transfer reaction of phospholipid methyltransferase II. Labeling of phosphatidylcholine was not affected, however. Dietary supplementation with 2% choline reduced liver methyltransferase activities of both control and ethanol treated mice. The ethanol induced increase in methyltransferase activity returned to control values upon removal of ethanol from the diet for 24 hours. It is suggested that the increase in phospholipid methyltransferase activity after chronic ethanol treatment may be responsible, in part, for alterations in the activities of certain microsomal enzymes known to be influenced by ethanol.

Previous results from this laboratory have shown that the progeny of alcoholic rats have diminished alpha 1-adrenergic receptors in the hepatic plasma membranes. Since these receptors mediate epinephrine action on glycogen metabolism, it was decided to determine whether this change might affect the activation of glycogen phosphorylase a in the livers of the alcoholic progeny. Pregnant female rats were divided into two groups of which one received a Metrecal-ethanol liquid diet throughout pregnancy and lactation. The pair-fed control group received a liquid sucrose-Metrecal diet over the same period. Phosphorylase a activity was determined in liver slices from the progeny during postnatal development. The basal hepatic phosphorylase a activity was identical between the control and experimental groups at 5, 15 and 25 days of age. Both epinephrine and phenylephrine were superior enzyme activators than was isoproterenol. Stimulation with epinephrine (10 microM) demonstrated a significantly diminished capacity of the enzyme in the alcoholic liver to be activated by the hormone. In every instance, the livers from 5, 15 and 25 day old pups from alcoholic mothers displayed diminished epinephrine-stimulated phosphorylase a activity of about 30%, compared with the controls.