PubMed Health⌕ Search

Biomedical subjects

H Kalant

Publications and source records attributed to H Kalant.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1976

Acquisition and loss of behaviorally augmented tolerance to ethanol in the rat.

The phenomenon of behavioral augmentation of tolerance (BAT) to ethanol (EtOH) in the rat was replicated in studies using the moving belt test of intoxication. Rats performing the test daily under the influence of EtOH (2.2 or 2.5 g/kg i.p.) developed tolerance more rapidly than those receiving the same dose after each daily session on the belt. However, both groups reached the same maximum level of tolerance. Acceleration of tolerance by BAT was proportional to the frequency of performance under the influence of EtOH when total exposure to EtOH was held constant. The degree of tolerance produced by BAT could not be increased by daily gavage with a large dose (6 g/kg) of EtOH. After termination of EtOH administration, tolerance produced by BAT was lost at the same rate, whether or not daily alcohol-free sessions on the belt test were given. These findings are consistent with the hypothesis that BAT and conventionally produced tolerance differ only in rate.

Animals↗
PubMed1976

Interaction of propranolol and phentolamine with ethanol in the rat.

The possible role of the adrenergic nervous system in the intoxicant effects of ethanol was examined in studies of the interaction or propranolol and phentolamine with ethanol. Propranolol teneded to increase the effect of lower doses of ethanol in a dose-dependent manner. However, the effect of higher doses of ethanol (over 2.0 g/kg) tended to be diminished by low doses of propranolol, whereas higher doses of propranolol were ineffective or actually increased the ethanol effect. Phentolamine tended to decrease the effect of the lower ethanol doses. These findings are inconsistent with any simple adrenergic mechanism in the mediation of the intoxicant effect of ethanol.

Animals↗
PubMed1976

Protection by propylthiouracil against carbon tetrachloride-induced liver damage.

Rats given a single intragastric dose of carbon tetrachloride (CCl4), 0.25, 0.50, or 1.0 ml per kg) showed a dose-dependent increase in SGOT, serum ornithine carbamyltransferase, and liver necrosis (graded histologically as 0 to 4+) 24 hr after the treatment. Daily intubation with propylthiouracil (PTU) for 10 days in doses of 5 to 50 mg per kg significantly reduced the elevation of SGOT activity, completely suppressed the serum ornithine carbamyltransferase changes, and reduced the degree of necrosis found 24 hr after the intragastric administration of CCl4. Similar protection was found when CCl4 was given intraperitoneally. When PTU was given in liguid diets for 6 days, protection against CCl4 was increased. PTU did not affect the absorption or covalent binding of 14CCl4 to lipids or proteins. Also, control and PTU-treated rats did not differ with respect to glucose-6-phosphatase activity and conjugated diene production after CCl4. Thus, it has been observed that PTU affords partial protection against some end-stage consequences of CCl4 liver injury such as cell necrosis and release of intracellular enzymes. However, PTU afforded no protection against early chemical effects such as covalent binding of CCl4 carbon, lipid peroxidation, or loss of glucose-6-phosphatase. Therefore, it is concluded that the mechanism of the PTU effect comes into play after the initial effects of CCl4 are exerted and in some unknown manner modulates the expression of these early effects.

Animals↗
PubMed1975

Effect of p-chlorophenylalanine on the acquisition of tolerance to ethanol and pentobarbital.

Rats were rendered tolerant to ethanol or pentobarbital by daily oral administration. Motor impairments after test doses of ethanol or pentobarbital were measured prior to and at various times during chronic treatment in order to assess the degree of tolerance development. Chronic administration of p-chlorophenylalanine (p-CPA) in a dosage regimen which produced and maintained approximately 95% depletion of brain serotonin (5-HT) did not alter motor impairment after initial acute administration of ethanol or pentobarbital. However, the rate of tolerance development to the motor-impairing effects of both drugs was slowed down in p-CPA-treated rats, p-CPA did not appear to exert this effect by altering the disposition of ethanol or pentobarbital, since blood levels determined 20 min after administration of the test doses were similar in animals treated with p-CPA and in controls. These findings suggest that brain 5-HT may have a role in tolerance development to ethanol and pentobarbital.

Animals↗