Substance and alcohol actions/misuse最新文献

This study was carried out to determine whether hepatic triglyceride (TG) synthesis is a major determinant in the development of fatty liver induced by chronic ethanol ingestion. For this purpose, the degree to which the 2-monoglyceride (MG) backbone of dietary fat was retained in the accumulated TG of fatty liver was examined. Triglycerides were isolated from diet and from the liver and plasma of rats maintained for four weeks on a Lieber-DeCarli liquid ethanol diet. Pancreatic lipase hydrolysis of the TG from these three sources was carried out and the MG produced was analyzed for the fatty acid composition. Almost all of TG in fatty liver and that released to plasma retained the MG structure which originated from diet fat. This result demonstrates that the de novo glyceride synthesis or transacylation reactions do not have a major role in the production of TG in alcohol-induced fatty liver.

Methadone maintenance patients who maintained on a high daily dose were divided into good performers and poor performers based on whether they demonstrated persistent use of heroin, non-prescription diazepam, and/or excessive alcohol consumption. Mean methadone plasma levels 24 hours after an oral dose of 80 mg were found to be 410.4 ng/ml in good performers compared to 101.8 ng/ml in poor performers (P less than .05). Seven of nine (77.8%) poor compared to two of 15 (13.3%) good performers had 24-hour methadone plasma levels under 50 ng/ml (P less than .01). High dose methadone patients who show evidence of persistent drug or alcohol abuse should have their 24-hour methadone plasma level determined to help assess whether the patient should receive more methadone or find an alternative treatment.

Pretreatment with doses of the amino acid, L-tryptophan, known to increase brain serotonin levels, markedly reduced the number of intravenous self-injections of d-amphetamine in rats previously demonstrating stable self-administration patterns. This attenuation of response was dose dependent in both magnitude and duration. Pretreatment with L-tryptophan did not alter the response rate in animals trained on an FR-40 food reinforced paradigm. L-tryptophan administration did not alter the apparent turnover of dopamine in nucleus accumbens septi, important since manipulation of dopamine in this brain area exerts a marked influence on psychomotor stimulant self-administration. These results are consistent with previous reports suggesting a role of serotonergic neurons in the self-administration of d-amphetamine.

Intellectual dysfunction, usually involving short-term memory, abstract reasoning, visuomotor coordination, intellectual flexibility, and spatial reasoning, is a well-documented finding among alcohol imbibers of various drinking styles. Despite the diversity of groups examined and the attempted control of variables other than alcohol consumption, little concensus has been reached with regard to the chronology of dysfunction (as related to lifetime drinking style, duration of alcoholism, quantity consumed per session, or type of potable). In many instances, diet, age, and even sex have outweighed the relative influence of alcohol in the degree of intellectual dysfunction. Morphologically, brain changes tend to be in the anterior/basal areas and may involve the third ventricle, diencephalic areas, and other focal variations. Cerebellar changes also are not uncommon yet may reflect a subgroup of alcoholics rather than a generalised trend. Generally, many intellectual deficits partially rebound rapidly within the first two or three weeks after cessation of drinking, with perhaps modest further improvement if sobriety is sustained for several months. Because of the extreme heterogeneity of the alcoholic population and the potent effect of ancillary variables upon measures of intellectual functioning, control and matching of demographic factors is a paramount consideration. Demographic variables of primary concern include age, sex, socio-economic status, education, duration of alcoholism, quantity of alcohol consumed per session, diet, psychotropic medications, secondary psychiatric diagnoses, secondary medical diagnoses, exact duration of abstinence, and prior exposure to psychometric instruments.

Numerous studies indicate that alcoholism runs strongly in families. Recent evidence from twin and adoption studies suggest the illness may have a genetic component. These studies have stimulated two lines of research which are actively being conducted in several centers. One type of research involves comparing alcoholics with a positive family history of alcoholism with alcoholics who lack such a history. The second line of research involves comparing college-age sons of alcoholics with sons of nonalcoholics before members of either group have had an extensive drinking history. Studies consistently show that "familial" alcoholics differ from "nonfamilial" alcoholics in having (a) an earlier age of onset and (b) symptoms of greater severity. Familial alcoholism has also been associated with a childhood history of hyperactivity and conduct disorder and an adult history of antisocial behavior. In one study, familial alcoholics more often showed signs of structural and functional brain abnormalities than did nonfamilial alcoholics. Sons of alcoholics versus controls have been reported to have higher blood acetaldehyde levels after drinking alcohol and also demonstrate more subjective and motor tolerance for alcohol. Sons of alcoholics also generate more alpha activity on the EEG after alcohol and make lower scores on the categories test of the Halstead Battery. About half of hospitalized alcoholics have a family history of alcoholism. Studies indicate that the family-history-positive and family-history-negative alcoholics differ on a number of variables. Twin, adoption and high-risk studies add further evidence that "familial alcoholism" is a separate diagnostic entity.