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Biomedical subjects

H Kalant

Publications and source records attributed to H Kalant.

At least 163 records · Page 9Linked to original sources
PubMed1978

Accelerated development of tolerance during repeated cycles of ethanol exposure.

Adult male rats were subjected to 1--4 cycles of daily gastric intubation with ethanol (6 g/kg) for 16 days, separated by 17-day alcohol-free periods. Tolerance produced by this treatment (designated 'physiological tolerance') was measured by change in effect of a 2.2 g/kg i.p. dose of ethanol on the moving-belt test. It occurred in each cycle, disappeared completely in the drug-free periods, and developed more rapidly in the second and later cycles than in the first. Tolerance produced by the 'behavioral augmentation' technique (daily test practice under the influence of ethanol) also developed more rapidly on a second than on a first cycle. The progression from within-session to between-session tolerance was still evident, but accelerated. With 25-day alcohol cycles, separated by a one-month drug-free period, the 'carry-over' effect (i.e., more rapid acquisition of tolerance in the second cycle) applied equally, regardless of whether or not tolerance was produced by the same technique in both cycles, or by a crossover in either direction between the two techniques.

Animals↗
PubMed1978

Effect of p-chlorophenylalnine on the loss and maintenance of tolerance to ethanol.

Rats were rendered tolerant to the motor-impairing effects of ethanol by daily oral administration. Subsequently, ethanol was withdrawn and the effect of p-chlorophenylalanine (p-CPA) on tolerance loss was examined. In two separate studies it was demonstrated that p-CPA, in a dosage regimen that produces extensive depletion of brain serotonin (5-HT), accelerated tolerance loss. These experiments suggest that at least part of p-CPA's inhibitory effect on net tolerance development to ethanol can be accounted for by its accelerating effect on tolerance loss; however, an inhibitory effect on tolerance acquisition cannot be excluded. On the other hand, once tolerance was established, p-CPA did not affect the maintenance of tolerance to ethanol.

Animals↗
PubMed1978

Effect of vasopressin-like peptides on consumption of ethanol by the rat.

Rats were trained to accept ethanol in their drinking water, by successive small increments or decrements in alcohol concentration in response to the individual consumption of each rat. Those injected with desglycinamide9-lysine8-vasopressin (DGLVP), 1--4 microgram SC every second day, attained almost twice as high a final acceptance concentration (FAC) and mean daily ethanol intake (g/kg) as vehicle-treated controls. Hypophysectomized animals initially accepted the same alcohol concentrations as intact rats, but drank much larger volumes and correspondingly higher daily g/kg intakes. However, this was rapidly succeeded by rejection of all but very low concentrations, which was unaffected by DGLVP. During a subsequent free-choice period (water vs. ethanol at individual FACs), the groups maintained their relative positions with respect to ethanol intake. This was not altered by injection of vasopressin in the hypophysectomized rats, but was overcome by raising the alcohol concentration. The results suggest that vasopressin-like peptides facilitate acquisition of alcohol drinking behavior.

Alcohol Drinking↗
PubMed1978

Regional distribution of ethanol in the rat brain.

The regional distribution of ethanol in selected areas of the rat brain was studied after single intravenous and intraperitoneal injections. Ethanol concentrations (measured by gas-liquid chromatography) in cortex, striatum, and hippocampus were compared with arterial and venous blood alcohol concentrations. As previously reported, equilibrium between tissue and arterial blood occurred within 3 min and followed simple diffusion kinetics. At shorter time intervals (1 min) after injection, regional ethanol concentrations differed, possibly because of regional blood flow and tissue mass. Equilibrium between tissue and venous blood required 10--15 min and coincided with the disappearance of the arterial-venous difference. These findings suggest that tissue ethanol concentrations cannot be determined from venous blood samples until brain arteriovenous equilibrium has occurred. They also support the argument that alcohol concentrations in tissue perfusates do not necessarily provide a reliable guide to those in the tissue.

Animals↗
PubMed1977

Alcohol withdrawal syndromes in the human: comparison with animal models.

Alcohol withdrawal syndromes in humans lie on a continuum of increasing severity, from the acute hangover to delirium tremens. Early mild reactions consist primarily of hyperexcitability phenomena such as tremor, insomnia, hyperreflexia and hyperventilation. In more severe degree, the same process gives rise to hallucinations and seizures. These early reactions are mimicked closely by alcohol withdrawal signs in experimental animals. Late reactions in humans are characterized by marked sympathetic nervous system overactivity, profound disorientation and hallucinations. Analogous reactions have not yet been observed clearly in other species. The problem may be one of finding appropriate techniques for detecting such changes, rather than a true species difference in their occurrence.

Alcohol Withdrawal Delirium↗
PubMed1977

Ethanol metabolism, oxygen availability and alcohol induced liver damage.

The rates of ethanol oxidation in various species are linked to the rates of general metabolism, and more specifically that of O2 utilization by the liver. After chronic ethanol administration, increased oxidation of ethanol is accompanied by increased total hepatic O2 utilization, as studied in the whole animal, the perfused liver, and isolated liver slices. The correlation is particularly striking in the spontaneously hypertensive rat. This linkage makes the liver of the chronically ethanol-consuming rat abnormally vulnerable to hypoxic damage. Exposure to 5% oxygen atmosphere for 6 hours produced major elevations of SGOT and SOCT activities and marked centrilobular necrosis, in alcohol-treated animals but not in controls. The same differential susceptibility was found to acute anemia produced by bleeding. The possible relation of these findings to alcoholic liver damage in humans is discussed.

Alcoholism↗
PubMed1977

Effect of p-chlorophenylalanine on development of cross-tolerance between pentobarbital and ethanol.

Rats developed cross-tolerance to the motor-impairing effects of ethanol after daily oral administration of pentobarbital. Chronic administration of p-chlorophenylalanine (p-CPA), in a dosage regimen previously demonstrated to maintain extensive brain serotonin (5-HT) depletion, slowed down cross-tolerance development. p-CPA did not appear to exert this effect by altering the disposition of ethanol, since blood ethanol levels measured 20 min after ethanol administration were not affected by p-CPA treatment. This study extends our previous findings with respect to the inhibitory effects of p-CPA on tolerance development to ethanol and pentobarbital, and suggests that 5-HT may play a role in cross-tolerance development between ethanol and pentobarbital.

Animals↗
PubMed1976

Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds.

Ethanol (0.4 to 0.8 g/kg in 30 minutes) was given by mouth to 102 healthy young volunteers (37 Caucasian men, 21 Caucasian women, 20 Chinese men and 24 Ojibwa men). Venous blood concentrations of ethanol and acetaldehyde 60, 90, 120 and 150 minutes after the end of drinking were measured by gas chromatography. The calculated rates of ethanol metabolism in the Caucasian men and women did not differ, but the overall group means for subgroups of Caucasians (103.6 mg/kg-h), Chinese (136.6 mg/kg-h) and Ojibwa (182.7 mg/kg-h) with decreasing postabsorption values differed significantly from each other. Mean acetaldehyde values paralleled the rates of ethanol metabolism: Ojibwa, 14.6 mug/ml; Chinese, 10.0 mug/ml; and Caucasians, 9.4 mug/ml. The high rate of ethanol metabolism in Amerind subjects differs from previous findings. Habitual level of alcohol consumption, proportion of body fat and genetic factors appear to account for most of the group differences.

Acetaldehyde↗