Faculty Bibliography

Naltrexone, an oral opiate antagonist, was administered to nine patients with a diagnosis of Alzheimer's-type dementia (ATD) in a two-phase design: an open dose-ranging phase and a double-blind placebo-controlled trial for patients who showed improvement during the open phase. After a three day placebo (baseline) period, patients received increasing doses of naltrexone over two weeks up to a maximum daily dose of 100 mg. Assessments were made at baseline and at daily dose of 5 mg, 50 mg and 100 mg. Testing was done 2 to 4 hours after medication was administered. Any patient who showed cognitive/behavioral improvement on a given dose of naltrexone was then treated with this dosage in a double-blind crossover comparison to placebo. Criteria for inclusion in the double-blind phase consisted of improvement on three behavioral scales and at least one cognitive test on a given dose of naltrexone. Each double-blind phase followed a one-week washout and was two weeks long. Two of the nine patients demonstrated apparent cognitive enhancement on 100 mg daily of naltrexone and were then tested in the double-blind crossover period. Only one of these patients improved during active naltrexone administration. We conclude that the opiate antagonist naltrexone in a dosage range of 5-100 mg daily is not efficacious in ATD

Prostaglandin E1 (PGE1) and prostanoid precursor fatty acids enhance the acute sedative effects of ethanol in mice, and reduce the intensity of withdrawal after chronic exposure to ethanol. Aspirin, and other inhibitors of prostanoid synthesis, attenuate ethanol's sedative effects, and interfere with the beneficial effects of prostanoid precursors (but not of PGE1 itself) in withdrawal. Neither aspirin nor indomethacin administered alone affect withdrawal behavior. In contrast, ethanol impairment of rotorod behavior is not affected by prostanoid precursors nor by aspirin. These findings support a role for prostanoids as modulators (? mediators) of certain direct effects of ethanol and a role for prostanoid deficiency in the pathogenesis of withdrawal behavior

The effects of propranolol, 20 to 30 mg/day, on neuroleptic-induced akathesia were compared with those of lorazepam, 2 mg/day, and periods of no treatment. Raters were blind to treatment condition. As reported in prior open studies, propranolol was found to be dramatically effective in reducing akathesia induced by neuroleptic treatment

Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities

In the context of recent work showing numerous interactions between ethanol, essential fatty acids (EFA) and prostanoids, we have evaluated the effects of gamma-linolenic acid methyl ester (GLA 99%; 18:3, n-6), on hepatic pathology induced by ethanol in rats. Groups of animals were pair-fed an alcohol-containing liquid diet or an iso-caloric maltose-dextrin diet. Animals fed ethanol for ten days had markedly increased hepatic triglycerides and histological evidence of fatty liver. These effects were partially attenuated by administration of GLA during the period of ethanol administration

A series of studies was conducted to evaluate the effects of phosphatidylserine (PS) in aged Fischer 344 rats. No effects were observed in any of four psychomotor tasks in which aged rats normally show deficits, nor on measures of shock sensitivity. However, significant dose-related effects on retention of passive avoidance were observed when PS was given both 30 min prior to training and retention. Further, in a second experiment similar positive effects were observed when PS was given only 30 min prior to training, as well as only 5 min following training. These results suggest that one effect of PS may include an ability to enhance neural events involved in the encoding or consolidation of new information into memory