Neurochemical aspects of ethanol dependence and withdrawal reactions in mice.

Mice were made physically dependent on ethanol by a 3-day period of alcohol inhalation with small daily injections of pyrazole. During this treatment the concentrations of norepinephrine, dopamine and 5-hydroxytryptamine were increased in brain with concomitant decrease in gamma-aminobutyric acid, RNA and DNA. However, the monoamine concentrations showed complete regression to normal levels at the time of maximal withdrawal seizure when GABA level was still elevated above the control values. Brain RNA and DNA concentrations remained low at this period. During the recovery phase, the pattern of neuronal components was almost the same as was observed at maximal withdrawal seizures. Pyrazole by itself did not produce significant changes in concentrations of the neuronal components of brain.

Influence of fatty acids on pressor responses to catecholamines.

Lauric, Myristic and Palmitic acids had no appreciable effect whereas Stearic, Oleic and Linoleic acids caused some reduction in dog blood pressure. Pressor responses to epinephrine and nor-epinephrine were potentiated whereas the depressor response to isoproterenol was reduced during the infusion of fatty acids in dogs. ACTH alone, which causes mobilization of free fatty acids had no appreciable effect on blood pressure responses to catecholamines, however, its administration followed by salicylate produced marked potentiation of the pressor responses to epinephrine and nor-epinephrine; the depressor response to isoproterenol was reduced.

Effect of Krebs cycle metabolites on frog heart.

All the Krebs metabolites except pyruvate, lactate, acetate and succinate reduced the force and rate of myocardial contractions and also decreased cardiac output in frog. Succinate on the contrary was found to augment the rate and force of heart. The cardiac stimulation produced by epinephrine was reduced by fumarate, malate, oxaloacetate and alpha-oxoglutarate, whereas transaconitate and citrate produced only a slight inhibition. Pyruvate, lactate, acetate and succinate did not alter cardiac response to epinephrine.

The effect of acute bilateral adrenalectomy on vasopressor responses to catecholamines in dogs.

The effect of acute bilateral adrenalectomy on the pressor responses to adrenaline, noradrenaline and isoprenaline was studied in anaesthetized dogs. The responses to all the three catecholamines were reduced by adrenalectomy. Treatment with cortisone, cyclic AMP partially restored the responsiveness. Desocycorticosterone, aldosterone, hydrocortisone, phenylbutazone or infusion of either saline and noradrenaline failed to improve the impaired pressor responses seen in adrenalectomized dogs. Treatment with corticosterone alone. combined administration of aldosterone and hydrocortisone or cortisone followed by cyclic 3',5'-AMP also restored catecholamine responses amost to normal. The pressor responses to catecholmaines in dogs were also reduced by metyrapone-induced cortical insufficiency. Administration of corticosterone, cortisone or cyclic AMP slightly improved these responses; the recovery was not, however, as effective as that noted in the adrenalectomized condition.