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Biomedical subjects

H Kalant

Publications and source records attributed to H Kalant.

At least 181 records · Page 10Linked to original sources
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

Residual learning deficit after heavy exposure to cannabis or alcohol in rats.

Acute oral administration of cannabis extract to rats (tetrahydrocannabinol dose, 10 milligrams per kilogram) impaired maze learning. The impairment was more marked after ten daily doses of the same size. After 1, 2, or 3 months' pretreatment with the same daily dose, followed by a 25-day drug-free period, no residual learning impairment was found. However, 6 months of daily administration of cannabis (tetrahydrocannabinol, 20 milligrams per kilogram) or alcohol (6 grams per kilogram) produced significant residual impairment of learning of maze and motor coordination tasks, 2 months or more after the last drug administration.

Animals↗
PubMed1976

Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats.

Thirty adult male Wister rats were pretrained to criterion on the moving belt test, and then made tolerant to ethanol by daily administration of increasing doses over a period of 3 weeks. After a one-month recovery period, they were divided into 3 groups, subjected to bilateral frontal polar cortical ablations, sham-operation and no operation respectively. After postoperative recovery, the cycle of ethanol treatment and testing was repeated. Only the lesioned group failed to reacquire tolerance. A pilot experiment showed that occipital cortical ablations also prevented tolerance. In a second experiment 32 rats, which had similarly undergone and then recovered from an initial period of ethanol tolerance, were divided into 4 groups which received daily treatment with sucrose plus cycloheximide (0.3 mg/kg), sucrose plus saline, ethanol plus cycloheximide, and ethanol plus saline respectively. Only the ethanol plus saline group re-acquired tolerance. Tt is concluded that frontal polar cortical lesions and cycloheximide can both block the development of tolerance to ethanol in animals previously shown to be capable of developing such tolerance.

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

Generalization of behaviorally augmented tolerance to ethanol, and its relation to physical dependence.

Adult rats, required to perform a motor coordination task while under the influence of ethanol (2.2 g/kg) daily for 12 days, developed significant tolerance to the effects of ethanol, not only on this test but also on a food-motivated maze task. At the same time, they showed reduced shock threshold for production of a startle response, and reduced open field test scores 23 hrs after the last dose of ethanol. Other animals receiving the same dose of ethanol immediately after each training session on the coordination task, and others performing the task and receiving no ethanol, showed no tolerance on either test and no change in shock threshold or open field behavior. The results suggest that behaviorally augmented tolerance depends on basic neuronal adaptive changes indistinguishable from those accompanying physiological tolerance and dependence.

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↗
PubMed1975

Sensorimotor and physiological effects of various alcoholic beverages.

Effects of a standard dose of alcohol (1.3 g/kg) in the form of Canadian rye whisky, Canadian beer and a sparkling table wine were compared with those of a nonalcoholic carbonated control beverage. Sixteen young male and eight female subjects, all moderate drinkers, were tested in a Latin square design. Measurements were made on the pursuit rotor and quantitative Romberg tests, and of skin temperature, heart rate, malar flush and blood alcohol concentration during the prealcohol baseline period and at regular intervals over the 4-hour drinking period. The three alcoholic beverages produced blood alcohol curves that did not differ significantly. All three alcoholic beverages produced increasing sensorimotor impairment over time, which corresponded in degree to the increasing blood alcohol concentration. There were no significant differences between the three beverages on either the sensorimotor or physiological measures at any blood alcohol value. The results of this study indicate that the degree of impairment after alcohol ingestion in a socially relevant manner is not dependent on the type of beverage consumed, but only on the resulting blood alcohol concentration.

Adult↗
PubMed1975

Death in amphetamine users: causes and rates.

The world medical literature contains 43 reports of deaths associated with amphetamines in a 35-year period. These included seven cerebrovascular accidents, six sudden cardiac deaths, three cases of hyperpyrexia, eight poisonings of uncertain mechanism and seven cases of medical complications of intravenous injection; the remainder were of uncertain cause. In contrast, in Ontario alone, in 1972 and 1973 there were 26 deaths in amphetamine users, of which 16 were due to accident suicide or homicide. Of the remaining cases, two were cardiac, two hepatic and the rest were mixed drug overdose. Pulmonary granulomata, subacute hepatitis and other lesions resulting from intravenous drug use were common findings at autopsy. On the basis of the estimated number of regular users of intravenous amphetamine in Ontario, the mortality rate in such users is at least four times as high as in the general population of the same age, and is comparable to that in alcoholics and heroin addicts. However, the absolute number of alcohol-related deaths is far greater than the number of deaths in amphetamine or heroin users.

Adolescent↗
PubMed1975

Acute tolerance to ethanol in the rat.

Male Wistar rats were examined on the moving belt test at approximately 10, 30 and 60 min after administration of ethanol in doses ranging from 1.0-2.8 g/kg. Immediately after the test, each animal was sacrificed and ethanol concentrations were measured. The regression line of impairment as a function of brain alcohol concentration showed a progressive shift toward higher brain levels with increasing time after alcohol administration. The results confirm the existence of acute tolerance to ethanol, as defined by reduced impairment of function for a given blood level on the falling versus the rising arm of the blood alcohol curve. Confusion of interpretation due to arterio-venous differences in alcohol concentration was ruled out by simultaneous measurements in arterial blood and brain. Practice effects were ruled out by testing each animal only once.

Animals↗
PubMed1975

Electroencephalographic signs of ethanol tolerance and physical dependence in the cat.

Spontaneous electrical activity was recorded from three cortical and five subcortical sites, via permanently implanted electrodes, in five conscious, freely-moving adult cats. Initial observations were made during and after an intravenous infusion of ethanol, 1 g/kg. The animals then received ethanol by gastric intubation, in doses of 1.5 g/kg every 8, 12 or 24 h, for a period of 5 weeks. Electrical and behavioral observations were repeated on the day following the last gavage, before and during another intravenous infusion of ethanol 1 g/kg. All animals showed EEG changes which are interpreted as signs of tolerance to and dependence on alcohol. EEG changes appeared up to a day earlier than gross behavioral signs of alcohol withdrawal.

Action Potentials↗
PubMed1975

Effects of various psychoative drugs on the metabolism of delta-tetrahydrocannabinol by rats in vitro and in vivo.

Metabolism of 14C-tetrahydrocannabinol (14C-THC) by rat liver microsomal preparations in vitro was studied in the absence and presence of other psychoative drugs. Disappearance of 14C-THC, and changes in metabolite patterns as shown by thin layer chromatography, were studied. SKF 525-A, pentobarbital, phenobarbital and amphetamine all produced an apparently non-competitive inhibition of THC metabolism. The inhibition produced by meprobamate was at least partly competitive. Morphine and mescaline had no evident effect. SKF 525-A and the barbiturates markedly decreased the concentrations of all the major THC metabolites found in the incubation media. In contrast, none of the drugs tested in vivo, with the exception of SKF 525-A, had any effect on the biliary 14C-excretion or metabolite pattern, or on final tissue levels of 14C, when administered in doses comparable to those used for studies of interaction with THC in vivo. SKF 525-A, however, did markedly decrease the excretion of total 14C and alter the pattern of THC metabolities in the bile, and increased the final tissue 14C levels. It is concluded that in vivo interactions between THC and other psychoactive drugs are probably not explainable primarily on the basis of altered THC metabolism.

Animals↗