Substance and alcohol actions/misuse最新文献

The chronic consumption of alcohol has been correlated with the development of cardiomyopathy and dysrhythmias. These disorders may be secondary to changes in the outflow of the autonomic nervous system. This study looked at the changes in cardiac cell responsiveness to carbamylcholine (CBL) and the concentration of muscarinic receptors. The studies were carried out on hearts excised from male Long-Evans hooded rats, pair-fed on ethanol (E) or control (C) liquid diet. The ethanol diet supplied 35-39% of calories as ethanol. The studies were carried out after 8-10 wks or 18-20 wks on the diet. Ventricular muscarinic receptors were measured using (-)-[3H]quinuclidinyl benzilate (QNB). These studies showed no significant difference in muscarinic receptor concentration or the dissociation constant for [3H]QNB binding after 8-10 wks or 18-20 wks of E ingestion. Electrophysiologic studies of chronotropic responsiveness to CBL showed no significant difference between the E and C groups after 8-10 wks or 18-20 wks. The responsiveness of subsidiary pacemaker cells to CBL was not different between E and C groups at 18-20 wks. These data indicate that chronic E ingestion for up to 20 wks did not effect the cardiac muscarinic receptor concentration or cholinergic response.

Some earlier results have suggested a link between diabetes and voluntary ethanol consumption. Measurement of blood glucose levels now showed, however, that the AA line of rats developed for high alcohol intake is not diabetogenic. The alcohol-avoiding ANA line was somewhat more susceptible to streptozotocin-induced diabetes. Streptozotocin greatly increased blood glucose levels, water intake, and food consumption, but had no effect on the voluntary alcohol drinking of either AA or ANA rats. Normalization of blood glucose levels with insulin from osmotic minipump implants also failed to change their ethanol drinking. Thus, although the evidence from some other lines of rats and mice suggests that alcohol drinking is related to some forms of diabetes, the present results indicate that it is independent of the diabetes induced by streptozotocin and also of water and food intake regulation in this situation.

The content analysis of five-minute speech samples obtained from detoxified chronic alcoholic patients is a valid test for measuring cognitive impairment during the course of treatment. Such cognitive impairment scores six months after hospital discharge can be predicted using the variables of age, educational level, certain drinking patterns and cognitive impairment scores at the time of hospital admission. Patients who abstain for six months following hospital discharge have less cognitive impairment than those patients who resume drinking.

In summary, neuropsychological deficits (impaired cognitive and perceptual motor functioning) exist in many alcoholics. These deficits, are related to treatment benefit and outcome. In our male alcoholic population, the deficits seem remarkably resistent to attenuation even after 13 months in about 50% of the retested alcoholics, namely, those who resume drinking. The question of such alcoholics having pre-morbid cognitive deficits is an important problem to resolve. Studies of recovery heretofore have been based on the implicit assumption that the cognitive deficits are alcohol induced. From our data there is good reason now to suspect that certain cognitive deficits preceded the alcoholism especially those alcoholics who have a history of childhood hyperkinesis/minimal brain-damage syndrome or who have a history of familial alcoholism.

102 patients (41 women) who were enrolled in Appleton 's Outpatient Treatment service between June 1, 1977 and June 1, 1978 required transfer to an inpatient setting. This comprised 17% of all admissions. The entry records of these individuals were scored for the Missouri Alcohol Severity Scale by entering retrospectively the data collected on admission. When, some time after their entry to the outpatient service, these individuals were transferred to an inpatient setting, they became part of the study sample. A like number of controls was also scored for alcoholism severity. The controls remained in the outpatient program successfully. Comparing the score of transferees and controls, the individuals had a statistically significant higher score on the Missouri Alcohol Severity Scale when they had first entered the outpatient clinic (p + 0.03). With addition of other questions, the Appleton Modification, the probability of this happening by chance was 0.001. The data support the concept that inpatient units may play a meaningful role in the course of alcoholism treatment. High dropout rates from outpatient treatment were among the limiting factors of the outpatient setting.

The effects of delta 9-tetrahydrocannabinol (delta 9-THC) on endocrine responses of ovariectomized rats and intact male rats were investigated. In delta 9-THC treated ovariectomized rats, the mediobasal hypothalamic (MBH) LHRH and methionine-enkephalin (met-enk) contents were high compared to either vehicle or naloxone groups. However, delta 9-THC, when administered simultaneously with naloxone, failed to change MBH LHRH levels in the ovariectomized rats. This suggests that LHRH release from the MBH, which is normally accelerated by ovariectomy, is blocked by delta 9-THC and this inhibitory effect of delta 9-THC on LHRH release is reversed by naloxone, suggesting an involvement of endogenous opiate system. In a second experiment using intact male rats, delta 9-THC was administered at 2 mg, 15 mg, and 30 mg/kg body weight. The delta 9-THC decreased immunoassayable LHRH in anterior hypothalamus preoptic area (AHPOA) and MBH in a dose-related manner. Significant increases in serum corticosterone and decreases in serum testosterone were also observed in the rats due to delta 9-THC treatment. The met-enk content of AHPOA and MBH was significantly increased in delta 9-treated rats. The results of this study suggest that delta 9-THC may decrease biosynthesis and/or release of LHRH by partly interacting with the endogenous opiate system.

A diagnostic aid using routinely available blood chemistry batteries is being developed which shows promise for use in identification of individuals with drinking problems as well as in individuals having alcoholic and nonalcoholic liver disease. A statistically complex form of pattern recognition known as quadratic discriminant analysis is performed on common clinical laboratory tests such as total protein, total bilirubin, phosphorus, chloride, carbon dioxide, glucose, WBCs, RBCs, and MCV values. The relationship of each of the tests to each other is analyzed, providing a type of biochemical "fingerprint," such that any one test may not be unique. Rather, the interrelationships to one another provide a unique statistical profile of an alcoholic, or an individual with alcoholic or nonalcoholic liver disease.

The brain has a great cellular heterogeneity. It is one of the most membrane dense organs in the body. There are different kinds of movements within the membranes. These are influenced by the acute effect of ethanol, which gives rise to more fluid membranes. When the lipid milieu in which the proteins are embedded is disturbed, the properties of the enzymes and receptor proteins are altered. Fluid regions are more affected than rigid ones. In chronic alcoholism, selective vulnerability among the cells determines the final outcome and myelin seems to be reduced. Biochemical assays on humans are restricted to spinal fluid, where brain membrance molecules must be searched for.

The exposure in humans to ethanol or barbiturates during prenatal or neonatal development is common. There are indications that the magnitude of the resulting symptoms may be genetically determined. In the present article, an animal model was established for the study of the genetic determination of the neurosensitivity to ethanol and barbiturates administered during prenatal and/or neonatal development. Inbred C57BL/10 (C57) and DBA/1 (DBA) mice were employed in the ethanol studies and these strains and the outbred HS/Ibg (HS) were used in the barbiturate studies. Early ethanol administration induced a long lasting increase in the susceptibility to audiogenic seizures in both strains but to a greater degree in C57. Neuropharmacological studies implicated the serotonergic but not the noradrenergic system as mediating the early ethanol induced changes in audiogenic seizures. Open field activity was decreased but only in C57. Male agonistic behavior and predatory behavior were greatly reduced by early ethanol administration but mainly in DBA. Long term induction of the activity of the hepatic enzymes, alcohol dehydrogenase and microsomal ethanol oxidizing system, occurred in both strains after early exposure to ethanol. After early exposure to phenobarbital HS mice had long lasting increases in the susceptibility to audiogenic seizures and in the hippocampus related behaviors, spontaneous alternations and eight arm maze performance. The hepatic microsomal drug oxidizing system was induced in adult HS mice with early phenobarbital (PhB) exposure. Early PhB exposure also caused long term decreased sensitivity to ethanol narcosis and an accelerated acquisition to barbiturate tolerance, possibly mediated via a change in the sensitivity of the post synaptic dopamine receptors. Changes in the PhB treated offspring also included a reduction in the levels thyroid hormone. Early exposure to PhB resulted in a long term deficit in the area of brain layers, number of neurons, dendritic spines and the ultrastructure. Strain comparison suggested that DBA was less neurosensitive to early PhB administration than both HS and C57. It was concluded that genotype-environment interaction exists in the effect of drugs on the developing CNS.

Six different studies of social drinkers drawn from California, Oklahoma, Massachusetts and Michigan, using different methodologies, indicate a negative association between social drinking (specifically quantity of alcohol consumed per drinking occasion) and sober cognitive performance. This relationship prevails not only in men but also in women. The decrements in performance are greater in older than in younger individuals, and they are more evident in heavy than in light social drinkers. These findings do not necessarily indicate, albeit they do suggest, a causal link between social drinking and impairments in cognitive functioning. Additional questions raised in this review must be answered before a cause and effect relationship is established between social drinking and cognitive dysfunction.