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T Duka

Publications and source records attributed to T Duka.

66 records · Page 4Linked to original sources
PubMed1980

Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary.

Acute ethanol administration increased methionine-enkephalin (met-enkephalin) and beta-endorphin levels in distinct areas of the rat brain, whereas chronically supplied ethanol caused a depression of met-enkephalin and beta-endorphin levels in most of the brain areas investigated. The beta-endorphin content of the intermediate/posterior lobe of the pituitary of rats and guinea pigs decreased by 70%. Withdrawal of ethanol resulted in a complete recovery of endorphin levels in brain and pituitary within two weeks. Whether the observed alterations in endorphin concentrations are causally related to the primary mechanisms underlying alcohol dependence is uncertain, since no obvious signs of physical dependence were observed in treated animals.

Alcoholism↗
PubMed1980

Diazepam-induced release of opioid activity in the rat brain.

Acute intravenous injection of diazepam (2.5 mg/kg) in rats resulted in a moderate (2-fold) increase in pain threshold, as measured by the 'vocalization test'. This effect was not antagonized by naloxone (10 mg/kg, i.p.). However, pretreatment of the animals with the enzyme-inhibitor, bacitracin (50 micrograms, i.c.v.), dramatically enhanced the diazepam-induced antinociception. This increased effect was partially antagonized by naloxone, indicating an opioid-mediated mechanism as involved and further supports the hypothesis that benzodiazepine application may release opioid peptides in restricted areas of the CNS.

Analgesics↗
PubMed1980

Functional aspects of endorphins.

Radioimmunoassay of methionine-enkephalin, leucine-enkephalin and beta-endorphin were used in order to study the distribution and release of endorphins. The distribution pattern of enkephalin immunoreactivity in brain, including human brain, is quite different from that of beta-endorphin immunoreactivity. Separation of beta-endorphin and beta-lipotropin by column chromatography revealed that the contribution of beta-lipotropin to beta-endorphin immunoreactivity in brain is very small. In the anterior lobe of the pituitary both beta-endorphin and beta-lipotropin were found, whereas in the intermediate/posterior lobe almost all immunoreactivity was due to beta-endorphin; considerable amounts of enkephalin were also detected. Raising the concentration of potassium ions stimulated the release of met- and leu-enkephalin from striatal slices and the release of beta-endorphin immunoreactive material(s) from hypothalamic slices; both phenomena were dependent upon the presence of calcium ions. Studies of the release of beta-endorphin from isolated rat pituitaries revealed characteristic differences between the anterior and intermediate/posterior lobes; e.g., lysine vasopressin and extracts from the median eminence were highly effective in releasing beta-endorphin from the anterior lobe without affecting the release from the intermediate/posterior lobe; on the other hand, dopamine inhibited beta-endorphin release from the intermediate/posterior lobe without affecting release from the anterior lobe. Increased beta-endorphin levels were found after various stress conditions in rat plasma, as well as after treatment with metyrapone and vasopressin. In normal human plasma significant amounts of beta-endorphin were detected; increased levels were found in Addison's, Nelson's and Cushing's disease. Chronic opiate treatment of rats for 10 days did not affect brain levels of enkephalin or the beta-endorphin content of the hypothalamus, pituitary and plasma. Precipitated withdrawal decreased beta-endorphin in the anterior lobe and hypothalamus and increased beta-endorphin levels in the plasma. Long-term morphine treatment (30 days) decreased enkephalin and beta-endorphin content in some brain areas and in the intermediate/posterior pituitary lobe but not in the anterior lobe.

Animals↗
PubMed1979

In vivo receptor occupation by benzodiazepines and correlation with the pharmacological effect.

The existence of specific receptor sites for benzodiazepines has been well documented by in vitro binding studies. In this study, using a highly radiolabelled [3H]-flunitrazepam, we investigated the binding of benzodiazepines to their receptor sites under in vivo conditions. Tracer doses of [3H]flunitrazepam (0.001 mg/kg) were injected i.v. into mice and the concentration of the drug in the brain was monitored. The accumulation of [3H]flunitrazepam 20 min after injection was found to be highest in the hippocampus, cortex, hypothalamus; to be intermediate in the striatum, medulla oblongata/pons and midbrain and to be lowest in the cerebellum. This corresponds well with the different densities of benzodiazepine receptors which we found in in vitro studies, with the exception of medulla oblongata/pons and cerebellum. When increasing doses (0.01--10 mg/kg) of non-labelled benzodiazepine derivatives (flunitrazepam, clonazepam, the 3S and 3R enantiomers of 5-(o-fluorophenyl)-1,3-dihyrdo-1,3-dimethyl-7-nitro-2H-1,4-benzodiazepine-2-one, and chlordiazepoxide) were injected simultaneously with [3H]flunitrazepam, a dose-dependant, saturable and and stereo-specific decrease of [3H]flunitrazepam concentration in the mouse hippocampus was observed. The dose range in which the unlabelled benzodiazepines decreases the levels of [3H]flunitrazepam in the hippocampus corresponds closely to that which inhibited pentylenetetrazol- or picrotoxin-induced seizures, indicating that this in vivo method determines the occupation of pharmacologically relevant receptors.

Animals↗
PubMed1979

Rapid changes in enkephalin levels in rat striatum and hypothalamus induced by diazepam.

The acute treatment of rats with diazepam induces pronounced changes in brain enkephalin concentrations, as was estimated for methionine(met)-enkephalin and in some representative experiments for leucine(leu)-enkephalin, employing highly specific radioimmunoassays. Diazepam selectively increased the enkephalin concentrations in the hypothalamus by about 35%, and lowered it in the corpus striatum by roughly 25%; no changes could be detected in the medulla oblongata/pons or midbrain. The drug-induced changes displayed a rapid onset. Peak effects were reached by 2 to 5 min after injection. Changes observed in the hypothalamus were only short lasting and were apparently parallelled by diazepam concentrations in the brain, whereas the decrease in the striatum was of markedly longer duration. Presently, the mechanism underlying all these changes is unknown. Whereas an increase in enkephalin concentrations in the hypothalamus may be discussed in terms of the anti-stress effect of benzodiazepines, the observed drop in striatal enkephalin is not obviously to be correlated to behavioural changes induced by these drugs.

Animals↗
PubMedDate not supplied

Naloxone attenuates the anxiolytic action of diazepam in man.

The present study addresses the possible role of endorphins in mediating the anxiolytic properties of diazepam (DZM) in man. The ability of a low dose (0.4 mg. i.v.) of the specific opiate antagonist, Naloxone (NLX) to modify the anxiolytic action of DZM (0.07 mg/kg i.v.) in 22 patients anticipating minor orthopaedic surgery was evaluated. The study was performed in a double-blind placebo (saline)-controlled, randomized design. DZM administered 3 hours pre operation, reduced the anxiety experienced by subjects as estimated on a formal rating scale completed by the patients. NLX, as compared to saline, given 30 min post DZM significantly and strongly attenuated, but did not abolish this effect of DZM. These findings parallel observations in rats of the ability of NLX to block the action of DZM in the conflict test and suggest that the anxiolytic action of DZM in man may be partially mediated by endorphins.

Adult↗
PubMedDate not supplied

Patterns of alcohol drinking in a population of young social drinkers: a comparison of questionnaire and diary measures.

Studies of alcohol use often depend on self-reported alcohol intake measured by quantity/frequency questionnaires. Previous research has shown that alcohol consumption may be underestimated by this type of retrospective questionnaire. The primary aim of this study was to compare the accuracy of an Alcohol Use Questionnaire (AUQ) with a 4-week diary account. A further aim was to explore patterns of drinking in young social drinkers, with particular attention to binge drinking, which has been suggested as a factor in increasing the risk of alcohol dependency. University students completed the AUQ in the laboratory. They were then asked to keep a record of their alcohol, nicotine and caffeine consumption over a 4-week period (diary). The questionnaire and the diaries were compared on factors of alcohol intake (units per week) and patterns of drinking behaviour (speed of drinking, number of times being drunk and percentage of times getting drunk when drinking). The two measures (AUQ and diary) were highly correlated on alcohol consumption and the other questions relating to drinking behaviour. However, differences were found between the two measures on alcohol intake, speed of drinking (drinks per hour) and number of times being drunk. Alcohol consumption was underestimated by approximately 12% on the questionnaire, and, when the accuracy of estimation of drinking habits was examined, it was found that high drinkers tended to underestimate their drinking behaviour, whereas lower drinkers tended to overestimate. The results suggest that the AUQ can be used with a reasonable degree of confidence, bearing in mind the tendency for high drinkers to underestimate consumption and drinking behaviour. Relationships between 'binge scores', beverage specificity and alcohol consumption support the idea that the criteria for binge drinkers should be based on patterns of drinking rather than alcohol consumption.

Adolescent↗