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Biomedical subjects

D B Goldstein

Publications and source records attributed to D B Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1979

Quantitative comparison of physical dependence on tertiary butanol and ethanol in mice: correlation with lipid solubility.

Mice were made physically dependent on t-butanol and the withdrawal reaction was compared quantitatively with that produced by ethanol. The mice inhaled t-butanol vapor (50-140 mumol/1 of air) continuously for 1, 3, 6 or 9 days. Daily t-butanol blood levels were determined by gas chromatography, using ethanol as internal standard. After t-butanol exposure the mice were removed from the vapor chamber and the withdrawal reaction was quantitated by hourly scoring of convulsions elicited by handling. The peak of the withdrawal reaction occurred 3 to 5 hr after the mice were removed from the t-butanol vapor. The intensity of the withdrawal reaction increased with the duration of inhalation, and with the t-butanol blood levels maintained during the intoxication period. The withdrawal syndrome was qualitatively similar to that produced by ethanol. Quantitatively, t-butanol was 4 to 5 times more potent than ethanol in producing physical dependence. Since t-butanol is about 4 to 5 times more lipid soluble than ethanol, the data are consistent with a cell membrane site for alcohols in producing physical dependence.

Alcoholism↗
PubMed1979

Additive physical dependence: evidence for a common mechanism in alcohol dependence.

In previous studies we demonstrated that mice could be made physically dependent with 3 or 6 days inhalation of t-butanol or ethanol vapor. In the present experiments the mice were treated with 3 days of t-butanol followed immediately by 3 days of ethanol at equipotent concentrations, for a total of 6 days continuous exposure. Other mice were given these alcohols in the reverse order. Withdrawal reactions, quantitated by scoring convulsions elicited by handling, were equivalent to those resulting from 6 days exposure to either alcohol alone. One alcohol not only substituted for the other in the maintenance of dependence, but also augmented the abstinence syndrome produced by the first 3 days exposure. An additive effect of ethanol and t-butanol in producing a withdrawal reaction is consistent with the hypothesis of a single underlying mechanism for producing physical dependence on alcohols. This experimental model may be useful for studying cross-dependence.

Alcoholism↗
PubMed1978

Increased cholesterol content of erythrocyte and brain membranes in ethanol-tolerant mice.

Mice were treated with ethanol for eight or nine days, using a liquid diet regimen known to produce physical dependence. In previous experiments, synaptosomal plasma membranes and erythrocyte ghosts from such ethanol-treated animals were found to be resistant to the fluidizing effects of ethanol in vitro, as measured by electron paramagnetic resonance. In the present experiments, corresponding membranes were analysed for phospholipid and cholesterol. The ratio of cholesterol to phospholipid was found to be significantly increased in both types of membrane after chronic ethanol treatment. The changed ratio was produced by an increase in cholesterol. There was little or no change in phospholipid content of the membranes. Increased cholesterol may explain the previously observed alteration of physical properties of the membranes.

Animals↗
PubMed1978

Osmotic minipumps for administration of barbital to mice: demonstration of functional tolerance and physical dependence.

Sodium barbital was administered to mice at a constant rate by miniature osmotic pumps implanted subcutaneously. Each pump delivered approximately 0.25 mg/hr. With two pumps per mouse, blood barbital levels of 20 to 30 microgram/ml could be maintained for various periods. Barbital was assayed by gas chromatography. Functional tolerance was shown by a significant decrease in sleep time after a challenge dose of barbital administered 24 hours after withdrawal. Physical dependence was demonstrated by withdrawal hyperexcitability as measured either with pentylenetetrazol or by convulsions elicited by handling.

Animals↗
PubMed1977

Drug tolerance in biomembranes: a spin label study of the effects of ethanol.

Ethanol in vitro increased the fluidity of spin-labeled membranes from normal mice. Membranes from mice that had been subjected to long-term ethanol treatment were relatively resistant to this fluidizing effect. The data suggest that the membranes themselves had adapted to the drug, a novel form of drug tolerance.

Adaptation, Physiological↗
PubMed1977

Circadian rhythms of ethanol consumption by mice: a simple computer analysis for chronopharmacology.

On the assumption that a sinusoidal curve adequately described the circadian rhythm of food or fluid consumption by mice, the whole daily pattern can be derived from a few observations. Examples are presented to show that the assumption is valid. This simple curve-fitting by computer is also applicable to analysis of blood levels of drugs administered in the food or drinking fluid. The method should be useful for estimating the magnitude of daily fluctuations in pharmacological variables, including drug intake rates and circulating drug levels.

Alcohol Drinking↗
PubMed1977

Temporal patterns of voluntary alcohol intake.

This paper describes methods of analysing temporal patterns of alcohol consumption by mice over time-courses of days or hours. Records of daily alcohol intake can be used to identify brief periods when the mice sobered up. These one-day 'breaks' apparently allow the previously acquired level of physical dependence to decay. Effective alcohol intake, calculated by taking account of breaks, is a good indicator of physical dependence. More detailed time studies show the circadian rhythm of intake and of blood alcohol levels. To analyse our records of alcohol consumption over successive 8-hour periods, we fitted the data to cosine curves. These curves show the amplitude of the intake rhythm, which in turn determines the stability of blood alcohol levels. The highest and most stable blood alcohol levels were obtained by administering alcohol in a liquid diet to individually-housed mice.

Alcohol Drinking↗
PubMed1977

Electron paramagnetic resonance studies of ethanol on membrane fluidity.

An optimum level of fluidity in the membrane appears to be important for some physiological functions. The present studies examined the effects of ethanol in erythrocyte and brain membrane preparations from Swiss Webster mice using electron paramagnetic resonance (EPR) techniques with a fatty acid spin label. The spectral parameter measured was the order parmeter, S, an index of membrane fluidity. Synaptosomal membranes were more fluid than myelin but less fluid than mitochondrial membranes. In low concentrations of 1 and 2 mg/ml of ethanol membrane fluidity was increased in mitochondrial, synaptosomal, and erythrocyte membranes. Dose-related increases in membrane fluidity were also observed at higher concentrations of 4, 8 and 16 mg/ml of ethanol for all of the membranes except myelin. These data indicate that non-lethal concentrations of ethanol may increase membrane fluidity in vivo.

Animals↗
PubMed1976

Drinking patterns as predictors of alcohol withdrawal reactions in DBA/2J mice.

Individually housed DBA/2J mice were fed a liquid diet in which ethanol supplied 33% of the calories. The level of physical dependence that developed was estimated by scoring convulsions, elicited by handling the mice, after discontinuing the alcohol diet. The severity of the withdrawal reaction increased progressively with duration (5-12 days) of alcohol administration. A 2-day period on the diet produced no withdrawal reaction. Pretreatment of the mice with alcohol in their drinking water slightly increased the subsequent intake of the liquid diet. "Effective" alcohol intake was defined as uninterrupted alcohol consumption above 10 g/kg/day. Withdrawal scores correlated better with effective intake than with total intake under a variety of conditions. We interpret this to mean that brief interruptions in drinking (1 day) may allow the accrued physical dependence to disappear. On the basis of their effective alcohol intake, mice could be assigned to nondependent, moderately dependent or severely dependent groups for further study of the nature of physical dependence.

Alcohol Drinking↗
PubMed1975

Alcohol withdrawal convulsions in genetically different populations of mice.

Individual Swiss-Webster mice differed in the intensity of their withdrawal reactions after a standard regimen of alcohol administration, and offspring resembled their parents in this respect. Inbred strains of mice also differed in the severity of their alcohol withdrawal reactions. C57BL mice showed almost no convulsions on handling. These results indicate that a genetic factor participates in determining the severity of alcohol withdrawal seizures in mice. The sensitivity to excitant actions of reserpine paralleled the sensitivity to alcohol withdrawal reactions in three strains of mice but not among individual mice of a genetically heterogeneous stock. The strain correlation between these traits was therefore fortuitous and does not demonstrate a common biochemical lesion in alcohol-withdrawn and reserpine-treated mice.

Alcoholism↗
PubMed1975

Physical dependence on alcohol in mice.

Although it has not yet been possible to construct a complete model of alcoholism in experimental animals; some aspects of the disease can now be studied with satisfactory laboratory systems. Production of physical dependence requires a period of continuous intoxication; brief intervals of sobriety allow the accrued dependence to disappear. Administration of ethanol by inhalation, with daily injections of pyrazole, allows maintenance of stable blood alcohol levels in mice. In this model, physical dependence arises to its maximum in a week or two and can decay in less than a day. Sedative drugs suppress the mouse withdrawal reactions but drugs that intefere with catecholamine or gamma-aminobutyric acid pathways facilitate withdrawal seizures. Susceptibility to withdrawal seizures is controlled in part by genetic factors.

Animals↗
PubMed1975

Drug dependence as an adaptive response: studies with ethanol in mice.

When mice were kept continuously intoxicated by inhalation of ethanol, physical dependence developed progressively, reaching its maximum in about 2 weeks. Decay of physical dependence during periods of sobriety was complete in about a day. These rapid time courses are consistent with a theoretical model in which alcohol inhibits and simultaneously stabilizes its target. This target may be located in central adrenergic synapses, because interference with function of such synapses facilitated the alcohol withdrawal reaction and because strain differences in withdrawal seizure scores correlated well with strain differences in reserpine effects.

Adaptation, Physiological↗