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Biomedical subjects

R A Deitrich

Publications and source records attributed to R A Deitrich.

At least 73 records · Page 4Linked to original sources
PubMed1981

Neurobiological and genetic aspects of the etiology of alcoholism.

In contrast to humans, most animals will not voluntarily consume alcohol to the point of intoxication nor to the point of development of tolerance and physical dependence. Since there is good evidence for a genetic component to human alcoholism, we explore the possibility that the presence of alcohol in the environment during human evolution has contributed to this difference in behavior from that observed in lower animals. We then review the biologic basis for genetic influences on various aspects of alcohol-related behaviors in both humans and lower animals. Thus, the evidence for genetic influences on rate of alcohol metabolism, preference, central nervous system depressant effects. tolerance, and dependence are briefly reviewed. The technique of selective breeding for alcohol-related behavior is described and compared to the process of natural selection that may be occurring in the human population.

Acetaldehyde↗
PubMed1980

A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats.

It has been reported that certain tetrahydroisoquinoline compounds, especially salsolinol and tetrahydropaveroline (THP) when infused into the lateral ventricle of rats' brains results in increased preference for alcohol solutions. The effect is reported to be long-term, in that animals do not return to baseline drinking even months later. The current report provides a replicatin of the original experiments and also an extension of the work to complete dose-response curves for salsolinol and THP. Generally we have confirmed that rats of the Sprague-Dawley and Long-Evans strains do increase their alcohol intake in response to infused THP or salsolinol and that the effect is long lasting, up to 10 months. Such animals consume less alcohol at concentrations above 20% than below, in contrast to the previous reports where drinking was maintained at high concentrations of alcohol. While the animals will select alcohol in the face of a saccharin choice, they will not drink alcohol adulterated with quinine. We have failed to observe signs of dependence or withdrawal by these techniques and suggest that the original reports of these signs may have been a result of cellular damage caused by the long-term infusions. Additionally we have carried out extensive dose-response experiments with both salsolinol and THP. Doses of THP of 104 nmoles/day were inhibitory to alcohol drinking. We conclude that these compounds do shift these animals preference for alcohol relatively permanently, but not to the point of gross intoxication nor into the highly aversive range of alcohol concentration. We cannot confirm the reports that salsolinol or THP produce withdrawal symptoms when infused.

Alcohol Drinking↗
PubMed1980

Evidence against a biphasic effect of acetaldehyde on voluntary ethanol consumption in rats.

A group of 27 male Long-Evans rats was given a 2 week period of free-choice ethanol and consumed 1.26 +/- 1.27 g/kg/day (mean +/- SD). The animals were then divided into 3 groups. One group received the aldehyde dehydrogenase inhibitor, cyanamide, in their diet and an oral ethanol dose of 2 g/kg for 5 days. Another group received only the oral ethanol dose and the third, control, group received no treatment during these days. After the forced cyanamide and/or forced ethanol treatment, all of the rats were returned to the choice situation. Voluntary ethanol consumption was then followed for 2 months, during which time the control rats steadily increased their ethanol intake to 3.6 +/- 2.1 g/kg/day (mean +/- SD of last week's consumption). The cyanamide treatment caused a transient (3--4 day) decrease in the ethanol intake, after which the consumption increased to 3.7 +/- 2.9 g/kg/day. Consumption by the forced ethanol group (5.4 +/- 2.0 g/kg/day) was significantly greater (p less than 0.05) than that by the other rats. The present results do not favor a physiological role for acetaldehyde-induced formation of alkaloids in increasing voluntary ethanol consumption, but do support the notion of an acetaldehyde-mediated aversive effect on ethanol drinking.

Acetaldehyde↗
PubMed1980

Characterization of acute and chronic tolerance in mice selected for inherent differences in sensitivity to ethanol.

Long sleep (LS) and short sleep (SS) mice have been selectively bred for differences in response to hypnotic doses of ethanol. In these studies, SS mice were found to develop functional tolerance faster than LS mice during a regimen of multiple injections of ethanol. No evidence for the development of acute tolerance was evident in mice of either of the selected lines or the offspring of an LS by SS cross (F1), and no metabolic tolerance developed during the 5-day alcohol treatment period.

Animals↗
PubMed1977

Role of liver cytosolic aldehyde dehydrogenase isozymes in control of blood acetaldehyde concentrations.

The role of various cytosolic aldehyde dehydrogenase (ALDH) isozymes in acetaldehyde metabolism was determined. Rats of known genotype (RR, reactor; rr, nonreactor) with respect to induction of a cytosolic enzyme by phenobarbital were used. Animals were treated with either phenobarbital (1.0 mg/ml in drinking water for 3 days) or 75 microng/kg (i.p.) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to ethanol treatment (2.5 g/kg). TCDD treatment is known to induce a second cytosolic ALDH isozyme in both RR and rr animals. Phenobarbital increased cytosolic ALDH activity 23-fold only in the RR animals, while TCDD increased activity 155-fold in both groups. Phenobarbital-treated RR rats maintained significantly lower blood acetaldehyde levels at 30, 90 and 150 minutes after ethanol injection compared to control RR animals. Blood acetaldehyde levels in phenobarbital-treated rr rats were not significantly different from rr controls. Administration of TCDD to RR or rr rats did not significantly alter blood acetaldehyde levels at 30, 90 or 150 minutes after ethanol treatment compared to appropriate controls. Similarly, phenobarbital significantly increased blood ethanol elimination rate (1.5 times greater than control) only in RR rats. Ethanol elimination rate was not significantly altered by TCDD in either group. Pargyline (100 mg/kg i.p.) did not significantly inhibit cytosolic ALDH activity, while total mitochondrial ALDH activity was inhibited by 28 and 57% in RR animals receiving TCDD and phenobarbital, respectively. Pargyline significantly increased blood acetaldehyde levels after ethanol administration. However, pretreatment with phenobarbital or TCDD significantly decreased elevated blood acetaldehyde levels resulting from pargyline treatment, with the greatest reduction in the phenobarbital-treated RR animals.

Acetaldehyde↗