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Abstract In patients with the carcinoid syndrome flushing provoked by intravenous noradrenaline, adrenaline, and dopamine, and by oral alcohol, was accompanied by a rise in bradykinin concentration in arterial blood. Flushing provoked by the catecholamines was blocked by intravenous phentolamine which simultaneously inhibited the rise in bradykinin concentration. Intravenous phentolamine in high doses also blocked flushing provoked by alcohol. The time sequence of alcohol-induced flushing and the inhibition of this flushing by α-adrenergic blockade suggests that alcohol might release a catecholamine which acts upon the tumour cell to release kallikrein.

It has been proposed that brain catalase plays a role in the modulation of some psychopharmacological effects of ethanol. The acute administration of lead acetate has dcmonstrated a transient increase in several antioxidant cell mechanisms, including catalase. In the present study, we investigated the effects of acute lead acetate administration on ethanol‐induced behavior, brain catalase activity, and the relation between both effccts. Lead acetate (100 mgkg) or saline was injected intraperitoneally in mice. At different intervals of time (1.3, 5, 7, 9, or 11 days) after this treatment, ethanol (2.5 g/kg) was injected intraperitoneally and the mice were placed in open field chambers. Results indicated that the locomotor activity induced by ethanol was significantly increased. Maximum ethanol‐induced locomotion increase (70% more activity than control animals) was found in animals treated with lead acetate 7 days before ethanol administration. Total brain catalase activity in lead‐pretreated animals also showed a significant induction, which was maximum 7 days after lead administration. A significant correlation was found between both effects of locomotor and catalase activity. In a second study, the effect of lead administration on d‐amphetamine (2.0 mg/kg) and tert‐butanol‐ (0.5 g/kg) induced locomotor activity was investigated. Lead acetatc treatment did not affect the locomotion induced by these drugs. These data suggest that brain catalase is involved in cthanol's effects. They also provide furthcr support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects.

Short-term and long-term effects of ethanol on the fatty acid composition of mitochondrial, microsomal and myelin fractions in brain have been investigated. Microsomal membranes were not modified by treatment for 60 hr, while in mitochondrial membranes there was a significant decrease in arachidonic and docosahexaenoic acids, responsible for the decrease in the double-bond index. A clear decrease in the 18:1/18:0 ratio was found in myelin after short-term treatment, whereas no significant variations were observed in the other subcellular membranes under the same conditions. On the other hand, chronic exposure to ethanol for 18 days induced a significant increase in oleic and docosahexaenoic acids in microsomal membranes. However, no significant changes were detected in the composition of fatty acids of mitochondrial membranes after 18 days of administration of ethanol. Contrary to that found with short-term treatment, a significant increase was observed in the 18:1/18:0 ratio of the myelin fraction after chronic consumption of ethanol. These results suggest that alcohol intoxication of neonatal chicks induces different modifications in composition of fatty acids of different membranes in the brain, those observed in the myelin fraction being specially important.

Concentrations of corticosterone in brain areas of TO strain mice were measured by radioimmunoassay. The studies examined the effects of routine laboratory maneuvers, variation during the circadian peak, adrenalectomy, social defeat and acute injections of alcohol on these concentrations. Brief handling of mice increased corticosterone levels in plasma but not in striatum and reduced those in the hippocampus. Single injections of isotonic saline raised the plasma concentrations to a similar extent as the handling, but markedly elevated concentrations in the three brain regions. Five minutes exposure to a novel environment increased hippocampal and cerebral cortical corticosterone levels and striatal concentrations showed a larger rise. However, by 30 min in the novel environment, plasma concentrations rose further while those in striatum and cerebral cortex fell to control levels and hippocampal corticosterone remained elevated. Over the period of the circadian peak the hippocampal and striatal concentrations paralleled the plasma concentrations but cerebral cortical concentrations showed only small changes. Adrenalectomy reduced plasma corticosterone concentrations to below detectable levels after 48 h but corticosterone levels were only partially reduced in the hippocampus and striatum and remained unchanged in the cerebral cortex. Single or repeated social defeat increased both brain and plasma concentrations after 1 h. Acute injections of alcohol raised the regional brain levels in parallel with plasma concentrations. The results show that measurements of plasma concentrations do not necessarily reflect the levels in brain. The data also demonstrate that corticosterone levels can change differentially in specific brain regions. These results, and the residual hormone seen in the brain after adrenalectomy, are suggestive evidence for a local origin of central corticosterone.

The effect of homeopathically potentiated ethanol (C30 and C200) on ethanol metabolism was studied in alcoholized rats. We measured ethanol concentration in the blood, alcohol dehydrogenase activity in the liver, and contents of biogenic monoamines in the hypothalamus, septum, and whole blood. Potentiated preparations of ethanol were efficient after long-term treatment and delayed ethanol elimination from the blood. Preparation C200 increased alcohol dehydrogenase activity. Potentiated preparations of ethanol (particularly C200) produced a positive effect on catecholaminergic and serotoninergic systems of the brain, i.e. they enhanced protective and adaptive reactions.

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans.

CRF is recognised for its actions on pituitary ACTH release, but also has direct effects within the brain which are important in mediating physiological responses to stress. Behavioral effects of CRF include increased locomotor activity and inhibition of food intake and its actions on metabolism are mediated mainly by activation of the sympathetic nervous system. CRF appears to be important in the regulation of energy balance and body weight, influencing both food intake and sympathetically-mediated thermogenesis. A defect in the synthesis or release of CRF has been implicated in the development of obesity in laboratory animals, since the condition is alleviated by adrenalectomy, hypophysectomy or exogenous CRF treatment. Recent data have revealed an additional role for CRF as a mediator of the neuroendocrine and metabolic responses to immune signals, particularly cytokines. The central actions of CRF are independent of the pituitary but may involve release of proopiomelanocortin products within the brain. CRF is thus emerging as an important integrator of the physiological responses to stress, infection and immunity, a finding which may have important implications for future therapies.