Substance and alcohol actions/misuse最新文献

Animals from two different populations of Wistar rats were chronically pretreated with naltrexone for 8 days. After a 2-day rest period, animals were tested with amphetamine for locomotor activity in the open-field with or without white noise (Day 2). The rats were similarly retested on Day 7 and Day 14. New colony animals showed a significant attenuation in amphetamine locomotor activity in the absence of noise only. In contrast, chronic naltrexone significantly decreased amphetamine activity in old colony animals only under noise conditions. The possibility of an inhibitory role opiate receptors on the dopamine neuro-transmission is discussed.

There are a variety of ways in which depression and alcoholism are related. These include the possibility of a person suffering from two relatively frequent diseases by chance alone. Secondly, on withdrawal from alcoholism depressive symptoms occur; these are rather short lived. Third, a secondary depression is seen in a large number of chronic alcoholics. Secondary depression is an ordinary depressive illness which manifests itself in the course of another primary illness, in this case alcoholism. There is no evidence that secondary mania exists to alcoholism. Finally, another type of relationship is familial. In a large number of alcoholics, such people come from families where depression also exists. This depression is called a depression spectrum disease. Depression spectrum disease is a depressive illness which occurs in an individual who comes from a family where alcoholism exists. Such a family may also contain other depressives but no manics. Depression spectrum disease patients are likely to have a relatively early onset, and are likely to show many problems in living and unstable personality characteristics. They are likely to be normal suppressors on the dexamethasone suppression test.

Methanol, ethanol, t-butanol and pentobarbital all produced marked dose dependent activation of locomotor activity in Short-Sleep mice which were selectively bred for relative insensitivity to the hypnotic properties of ethanol. The locomotor activity of alcohol sensitive Long-Sleep mice was depressed in a dose dependent fashion by all four drugs. Simultaneous assessment of intoxication in a grid test indicated that all four drugs disrupted coordination, in a dose dependent manner, to a greater degree in Long-Sleep mice than in Short-Sleep mice. The line differences in response to all alcohols was greater than for pentobarbital, indicating that the previous assumption of specificity of the selection for alcohols may be a question of degree rather than a qualitative effect.

Twenty-three blood constituents were analyzed in rats chronically injected with phencyclidine (PCP, angel dust). After receiving three injections weekly for an average of 9 months the only analyte to significantly change was creatine phosphokinase (CPK), which showed a threefold elevation over the saline injected controls.

The alcohol-addictive metabolite hypothesis of alcohol addiction is reviewed. The status of monoamine oxidase in this clinical condition is also discussed and possible reasons for low platelet activity proposed. An endogenous monoamine oxidase inhibitor, which is also a benzodiazepine receptor ligand, denominated tribulin, is produced in excess following alcohol withdrawal and may, in fact, be a predisposing factor for or the actual agent precipitating delirium tremens. Alcohol suppresses tribulin production and predisposed individuals may drink it to counter the dysphoric effects of a baseline overproduction of this compound.

The neurological complications of alcoholism are briefly mentioned. The cerebral dysfunction associated with long-term alcohol abuse is discussed in detail. The techniques used for measurement of functional deficits and cerebral morphological abnormalities are outlined. Significant correlations were noted between cerebral atrophy and functional measurements. Age was the most important covariate except in those alcoholics with the Wernicke's syndrome or an amnesic syndrome (with VIQ-MQ greater than or equal to 15). Partial reversibility of functional and cerebral atrophy measurements was noted in some recently abstinent alcoholics. EEG abnormalities also tended to improve in some alcoholics. A prolonged but resolving CSF acidosis was noted in many subjects. Possible biological mechanisms and the treatment implications of the sometimes slow (weeks to months) but remarkable functional recovery seen in some recently abstinent alcoholics are discussed.

It is well established that alcoholics have a very high suicide rate. The evidence is of two kinds: a) Follow up studies of alcoholics consistently reveal high suicide rates. The proportion dying by suicide varies from 8% (Kessel & Grossman, 1961) to 21% (Gabriel, 1935) depending on the length of follow up. These figures represent a risk 5080 times that of the general population. Most such studies were based on clinically identified populations of alcoholics and might not be representative of alcoholics in general. However: b) Retrospective studies of suicides consistently find that a high proportion (varying from 15% in southern England Barraclough et al., 1974 to 27% in Seattle Dorpat & Ripley, (1960) were alcoholics. The evidence of these retrospective studies is that suicide usually occurs at a late stage in the alcoholic career and is associated with things which are high risk factors for suicide in other settings e.g. divorce, a history of previous suicide attempts and increasing age. The origins of the close relationship between alcoholism and suicide have rarely been investigated, though the relationship is readily comprehended. Several elements probably contribute: 1. Alcohol dependence often leads to social decline-break up of marriage, loss of job and family ties-and the resulting social isolation is a potent cause of suicide. 2. Alcohol dependence leads to loss of self esteem and hence to depression and these psychological changes predispose to suicide. 3. Intoxication produces increased impulsiveness and a weakening of normal restraints against dangerous behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Two groups of rats were fed for 4 months either a lipotrope deficient (E-D) or a lipotrope supplemented (E-S) diet, both containing about 30% of total calories as ethanol (E). Two control groups consumed similar lipotrope deficient (S-D) and lipotrope supplemented (S-S) diets, but with sucrose (S) replacing ethanol. The rate of ethanol disappearance, microsomal protein content and total microsomal H2O2 generation were about 50% higher in the E-D group than in the other groups. Morphological studies revealed moderate to severe fatty changes only in the livers of the lipotrope deficient groups (E-D; S-D), while mitochondrial enlargement was observed only in the alcohol fed groups (E-S; E-D), particularly in the E-S group. State 3 respiratory rates with succinate and with malate-glutamate as substrates were about 50% reduced in the liver mitochondria of the animals of the E-S group, as compared with the other groups. From these results it is inferred that the lipotrope supplemented diet effectively prevented the alcoholic fatty liver but counteracted the alcohol-associated increases of ethanol oxidation rate, microsomal protein content and total microsomal H2O2 generation. On the other hand, the lipotrope supplemented diet was a necessary factor for the impairment of the mitochondrial respiratory function observed after chronic ethanol feeding.