Naloxone attenuation of voluntary alcohol consumption.

The effect of naloxone on voluntary alcohol consumption was examined in two lines of rats which have recently been selectively bred for oral alcohol preference (High Alcohol Drinking or HAD line) or aversion (Low Alcohol Drinking or LAD line). Genetic differences in brain met-enkephalin content were examined in two additional lines of rats which have been genetically selected for oral alcohol preference (Alcohol-Preferring or P line) or aversion (Alcohol-Nonpreferring or NP line).

Alcoholism: is it a model for the study of disorders of mood and consummatory behavior?

Depression, eating disorders, and carbohydrate craving are frequently seen in alcoholics or recovering alcoholics. Accordingly, these disorders may share some mediating pathways. It is now well-established that there is a genetic predisposition to alcoholism.

Alcohol preference and regional brain monoamine contents of N/Nih heterogeneous stock rats.

The N/Nih heterogeneous stock rats were tested for alcohol drinking behavior. Rats that met criteria for high (greater than 5.0 g ethanol/kg body weight/day) and low (less than 0.

The development of metabolic tolerance in the alcohol-preferring P rats: comparison of forced and free-choice drinking of ethanol.

Experiments were performed to determine whether metabolic tolerance to alcohol develops in the alcohol-preferring P rats during free-choice drinking. In Experiment 1, alcohol elimination rates (AERs) in female Wistar and P rats were measured as a function of age from 26 to 180 days old. AERs calculated as mmol hr-1 per kg body weight fell with age, whereas AERs expressed as mmol hr-1 per rat increased to reach a constant value after 60 days of age.

Effects of scheduled access on ethanol intake by the alcohol-preferring (P) line of rats.

The effects of scheduling the availability of ethanol on its voluntary consumption by the selectively bred alcohol-preferring P rats were examined under three conditions: unrestricted 24 hr/day access (Condition A), access limited to a continuous 4 hr/day (Condition B), and access limited to 1 hr every 3 hr, 4 times/day (Condition C). Food and water were always available. Daily alcohol intakes (mean +/- SEM) with Conditions A, B and C were 6.

Effect of low dose ethanol on spontaneous motor activity in alcohol-preferring and -nonpreferring lines of rats.

To determine if behavioral arousal may be associated with ethanol preference, the effects of low to moderate doses of ethanol on spontaneous motor activity (SMA) were studied in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats as well as in the Maudsley Reactive (MR/N) and Nonreactive (MNR/N) strains. Alcohol-naive rats had food and water available ad lib, but food was removed 24 hr before and during activity testing. After an intraperitoneal injection of saline (5 ml) or ethanol (0.

Effects of ethanol on monoamine and amino acid release from cerebral cortical slices of the alcohol-preferring P line of rats.

The effects of 250 mg/100 ml ethanol on the efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and the 35 mM K+-stimulated, Ca2+-dependent release of norepinephrine (NE), dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate, and aspartate from cerebral cortical slices of the alcohol-preferring P line of rats and stock Wistar rats were studied. The K+-stimulated, Ca2+-dependent release of GABA for the P rats was 35% lower, while the release of glutamate was almost twice that of the stock animals. The release of the other compounds was similar for the two groups.

Studies on an animal model of alcoholism.

Past and ongoing studies indicate that the selectively bred P line of rats satisfies virtually all the suggested criteria for an animal model of alcoholism. They attain pharmacologically active levels of BAC and develop tolerance and physical dependence with voluntary oral ethanol ingestion, while in the free-feeding state. Ethanol is positively reinforcing to the P rats and consumption appears to be directed by the post-ingestive, pharmacological effects of ethanol, as revealed by the intragastric self-administration studies.

Transport and metabolism of vitamins.

Although the biochemical roles of most vitamins in the body are reasonably well understood, our knowledge of how the body transports and metabolizes the vitamins is incomplete. This paper summarizes the information available on riboflavin, vitamin B-6, biotin, vitamin D, vitamin C, and pantothenic acid. As might be expected on the basis of the diverse chemistry and biology of these substrates, the body has quite unique mechanisms for handling each of them.

Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans.

Factors that regulate the clearance of plasma pyridoxal-P (PLP) are unknown. Four volunteers were given a diet supplying approximately 12 mumol pyridoxine (PN) per day. The pharmacokinetics of plasma PLP clearance were measured in these subjects before and after 4 weeks of intravenous PN supplementation (122 mumol/day).

Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential.

Since glucagon can hyperpolarize hepatic plasma membrane and stimulate biliary bile acid secretion in vitro, we studied the effect of glucagon on taurocholate uptake and its relationship to plasma membrane potential in isolated rat hepatocytes. [14C]taurocholate uptake was linear through 1 min and contained a saturable sodium-dependent and a nonsaturable sodium-independent component. Km of taurocholate uptake by the sodium-dependent system was 18.

The measurement of plasma vitamin B6 compounds: comparison of a cation-exchange HPLC method with the open-column chromatographic method and the L-tyrosine apodecarboxylase assay.

A cation-exchange high-performance liquid chromatographic (HPLC) method was found to be comparable to the open-column (OCC) method for measuring six different B6 compounds in human plasma and the L-tyrosine apodecarboxylase (LTD) assay for pyridoxal-P (PLP). Plasma samples were obtained from 9 subjects before and after 7 days of pyridoxine (PN) supplementation. PLP, pyridoxal (PL) and 4-pyridoxic acid (4-PA) were the major B6 compounds in plasma and the only compounds which increased after supplementation.

Regulation of the formation of stable adducts between acetaldehyde and blood proteins.

Recent reports have described increased levels of a fast-moving hemoglobin (Hb) fraction in alcoholic patients and formation in vitro of stable adducts between acetaldehyde and Hb as well as between acetaldehyde and albumin. In the present study, we have found that factors other than acetaldehyde concentration can influence the rate of stable adduct formation. HbAo was purified and its 2,3-diPglycerate removed by dialysis.

Monoamine uptake inhibitors attenuate ethanol intake in alcohol-preferring (P) rats.

The P line of alcohol-preferring rats drink pharmacologically significant amounts of ethanol when given free choice between a 10 percent ethanol solution and water. Serotonin (5-HT) uptake inhibitors and desipramine, a norepinephrine (NE) uptake inhibitor, were found to significantly reduce their ethanol consumption for up to 24 hours after intraperitoneal injection. To determine if this effect of 5-HT uptake inhibitors could be altered by receptor antagonists, some of which are short acting, P rats were trained to drink ethanol by free choice during scheduled availability, with ethanol being presented one hour every four hours during the light cycle.

Alcohol preference and voluntary alcohol intakes of inbred rat strains and the National Institutes of Health heterogeneous stock of rats.

The alcohol preference ratios and the daily free-choice ethanol intakes (10% ethanol versus water) of the newly constituted National Institutes of Health (NIH) heterogeneous stock (N/Nih) rats, and of the eight inbred strains from which N/Nih derived, were measured. Among the eight inbred strains, ACI/N, WKY/N, F344/N, BUF/N, BN/Ssn, WN/N, M520/N, and MR/N, the ACI exhibited the lowest preference and intakes and the MR and the M520 the highest. The mean values for the N/Nih animals were intermediate among those of the inbred strains.

Rate-determining factors for ethanol metabolism in fasted and castrated male rats.

The effects of castration and fasting upon the alcohol elimination rate, liver alcohol dehydrogenase (LADH) maximum activity (Vmax), and hepatic concentrations of ethanol, acetaldehyde, and free NADH during ethanol oxidation were examined in male Wistar rats. Castration increased the Vmax of LADH and, to a lesser extent, the alcohol elimination rate in vivo. On the other hand, fasting reduced the Vmax of LADH and the alcohol elimination rate in sham-operated and castrated rats but it did not nullify the effect of castration.

Intragastric self-infusion of ethanol by ethanol-preferring and -nonpreferring lines of rats.

An ethanol-preferring line of rats, developed by selective breeding, consumed as much as 9.4 +/- 1.7 grams of ethanol per kilogram of body weight per day through intragastric self-infusions, yielding blood ethanol concentrations of 92 to 415 milligrams per 100 milliliters.

Comparison of the use of L-tyrosine apodecarboxylase and D-serine apodehydratase for plasma pyridoxal phosphate assay.

The enzymatic methods for plasma pyridoxal 5'-phosphate (PLP) assay using L-tyrosine apodecarboxylase (apo-LTD) and D-serine apodehydratase (apo-DSD) were compared with respect to their operating characteristics, accuracy and precision. With the apo-LTD assay, the recovery of authentic PLP added to irradiated plasma was 96-100% and the precision for within-run and run-to-run replicates was 4-5% (coefficient of variation). The recovery of authentic PLP with the apo-DSD assay tended to be lower (viz.

Clearance and metabolism of plasma pyridoxal 5'-phosphate in the dog.

This study was undertaken to characterize the metabolic fate of plasma pyridoxal 5'-phosphate (pyridoxal-P), the role of various organs in mediating its degradation, and the contribution of urinary excretion. Anesthetized dogs underwent sham operation, hepatectomy, nephrectomy, or combined surgical removal of the stomach, small intestine, and the spleen; however, the kinetics of plasma pyridoxal-P clearance after the intravenous administration of 2.5 mg of this B6 vitamin were not altered.

Monoamine and metabolite levels in CNS regions of the P line of alcohol-preferring rats after acute and chronic ethanol treatment.

Levels of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 8 brain regions of the P line of alcohol-preferring rats following: (a) an IP injection of 2.5 g ethanol/kg body wt; (b) 8 and 15 weeks of chronic free-choice drinking of 10% ethanol; (c) 15 weeks of chronic free-choice drinking of 10% ethanol and 24 hours of withdrawal; and (d) 7 weeks of forced administration of 5% ethanol in liquid diet. One hour after IP injection of 2.

Initial sensitivity and acute tolerance to ethanol in the P and NP lines of rats.

We recently reported that selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats differ in sensitivity to a single sedative-hypnotic dose of ethanol, as measured by performance in the jump test. The present study examines the contributions of initial sensitivity and acute tolerance development to this difference. Initial sensitivity, assessed by brain alcohol content upon loss of the aerial righting reflex, was not significantly different between P and NP groups given 3 g ethanol/kg body weight intraperitoneally.

Intrahepatic cholestasis and sicca complex after thiabendazole. Report of a case and review of the literature.

Thiabendazole is a relatively safe and effective agent with a wide range of activity against nematodes infesting the gastrointestinal tract. A 55-yr-old man developed prolonged jaundice and sicca complex after a course of thiabendazole therapy. Endoscopic retrograde cholangiopancreatography demonstrated normal biliary tree and pancreatic ducts.

A blinded prospective study comparing four current noninvasive approaches in the differential diagnosis of medical versus surgical jaundice.

A prospective study was undertaken to compare the diagnostic accuracy of clinical evaluation, ultrasound, computed tomography, and technetium 99m-HIDA or -PIPIDA biliary scans in distinguishing between intrahepatic and extrahepatic jaundice. A final diagnosis was established in each of the 50 patients who completed the study, among whom 29 had intrahepatic cholestasis and 21 had extrahepatic obstruction. In the diagnosis of extrahepatic obstruction, the sensitivities of clinical evaluation, ultrasound, computed tomography, and nuclear medicine biliary scan were 95%, 55%, 63%, and 41%, respectively; the specificities were 76%, 93%, 93%, and 88%; and the overall accuracies were 84%, 78%, 81%, and 68%.