[Nutritional and genetic factors that influence the appetite for alcohol drinking].
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Biomedical subjects
Publications and source records attributed to J Mardones.
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Aminotriazole (1 g/kg IP) pretreatment resulted in higher ethanol blood levels during the first hour after 90 mmole/kg IP ethanol administration and at 1 hour after when rats received 60 mmole/kg IP, than the respective controls receiving the same doses of ethanol. No difference in the blood levels at time higher than 1 hour were observed, in spite of the fact that the inhibitory effect of aminotriazole lasted more than 7 hours. These results are consistent with the idea that hepatic catalase may play a significant role in liver first pass effect when portal blood levels are expected to be rather high, but not when distribution balance is established.
Blood ethanol levels registered in rats receiving 90 mmole/kg by gavage were not different in rats pretreated with aminotriazole (1 g/kg IP) 1 hour before, than in untreated controls. Results are consistent with the idea that no measurable gastrointestinal catalase first pass effect is present in rats.
The effect of pyrazole (35 or 70 mg/kg IP) on the voluntary consumption of ethanol, water and solid food was studied in UChA (genetically low ethanol consumer) and UChB (genetically high ethanol consumer) rats of both sexes, under a free choice of 10% v/v ethanol solution, distilled water and solid food. the data were analyzed according to the method previously proposed for recognizing the specific effect on appetite-satiety of ethanol. The effect of pyrazole in UChB rats correlated with the pattern of specific effects on appetite-satiety for ethanol. The only effect observed in UChA rats was a decrease in the intake of solid food and total water. No significant sex differences were observed.
The capacity of rat brain homogenates to oxidize ethanol by catalase peroxidative system, previously reported, was reevaluated in experiments using lower ethanol concentration, showing that the effect of this system can be observed even with a concentration of 50 mM, equivalent to non lethal blood level. The involvement of catalase was confirmed by its blocking by aminotriazole (AT) or methanol but not by pyrazole or butanol. Evidence for a functional role of ethanol oxidation by brain catalase in the action of this substance was given by the fact that rats pretreated with AT (1 g/kg IP) exhibited a significant shorter narcosis than untreated controls, strongly suggesting the mediation of acetaldehyde in this effect. Previous results with doses of 60 mmole/kg IP were confirmed with 70 mmole/kg IP, but not with 90 mmole/kg IP. A significant prolonging of narcosis time was observed when AT was administered after any of these doses by an unknown mechanism. Furthermore it was observed that AT pretreatment reduced significantly the lethal effect of 110 mmole/kg IP ethanol; but when AT was given after ethanol (90 mmole/kg IP) it enhanced the lethality. These results suggest that catalase peroxidative pathway might play a role not only in narcosis time but also in ethanol toxicity.
A method of mathematical treatment of data concerning changes in voluntary consumption of ethanol solution, water and solid food, induced by experimental treatments in animals, in order to recognize effects on mechanisms involved in specific appetite and satiety for calories, water and ethanol is proposed. The need of such method arises from the fact that several experimental treatments tested by the effects on ethanol consumption alter at the same time the appetite or satiety for calories and/or for water, as well as ingestive behavior. The results of testing the method with the data obtained by treatment of UChA and UChB rats with disulfiram or cyanamide were consistent with the expected ones.
The immediate and the long-lasting effects of PCPA (126 mg/kg IP for 3 days) on the voluntary consumption of 10% v/v ethanol solution, water and solid food were studied in genetically low (UChA) and high (UChB) ethanol consumer rats. Data were analysed according to the method proposed by the authors for recognizing specific effects on ethanol consumption. Results confirmed immediate specific decrease of ethanol consumption in UChB rats, while a nonspecific decrease of it was observed in UChA rats. In UChB rats ethanol consumption recovered the basic level about nine days after the first dose. By contradistincion, in UChA rats a significant specific increase of ethanol consumption, starting at the first week after the treatment, was observed. During this period 12 out of 21 UChA rats reached an ethanol consumption level commonly observed in UChB rats, and 10 of them recovered the pretreatment level in 15 to 30 weeks. The other 2 maintained the high consumption until 38 weeks of observation. At that time the serotonin content of cortex and hippocampus of these 2 rats was normal.
The effects of zimelidine, fluvoxamine, and citalopram (serotonin uptake blockers), as well as those of 5-hydroxytryptophan (serotonin precursor), on the voluntary consumption of 10% ethanol solution, distilled water and solid food were tested in UChA (genetically low ethanol consumer) and UChB (genetically high ethanol consumer) rats. Since it is well known that drugs which stimulate central serotonergic synapses decrease food and water intake, the data concerning the difference of the respective consumption during the treatment period and the pretreatment one were analysed with a method previously proposed (Alcohol 5:15-19; 1988) to recognize specific effects on ethanol intake. The results showed that while the decrease of ethanol consumption induced by the three serotonin uptake blockers appeared not to be specific of ethanol, the effects of 5-hydroxytryptophan in UChB rats satisfy the criteria for being considered as an expression of a decrease of the specific appetite--or increase satiety--for ethanol. Experimental results cannot help in the explanation of this difference.
Aminotriazole (AT), a catalase inhibitor, was administered to UChA (low ethanol consumer) and UChB (high ethanol consumer) rats. Ethanol, water, and solid food intake were measured during basic, treatment, and posttreatment periods. The effects of AT on brain catalase activity and acetaldehyde recovered during incubation of brain homogenates with ethanol were also studied in rats of both strains. Results showed that AT decreased voluntary ethanol intake in UChB rats, and also diminished the consumption of food by rats of both strains. No strain difference in brain catalase activity and acetaldehyde recovered during ethanol incubation was observed. The results suggest that AT effect on ethanol consumption is secondary to a reduction in the appetite for calories and not related to its catalase blocking effect.
The effect of bromocriptine (stimulant of dopaminergic D2 receptors) on the daily consumption of 10% v/v ethanol solution, distilled water, and solid food, under free-choice conditions, was measured in nine genetically low (UChA) and six high ethanol consumer (UChB) adult female rats. Animals were housed in individual cages and maintained at room temperature of 23 +/- 1 degree C and with 12/12 h dark/light rhythm. The consumption of ethanol solution, water, and solid food was measured in pretreatment, treatment, and posttreatment periods of 3 days (Tuesday through Thursday) of 3 consecutive weeks. During the treatment period rats received daily a single oral dose of 8 mg of bromocriptine mesylate (Sandoz) suspended in 1 ml of water per kg of body weight. Data analysis was performed with a method previously reported, which allows to recognize specific effect of ethanol intake, depurated from the effects on calories and/or water consumption. Results showed that all UChB rats decreased significantly and specifically the consumption of ethanol solution during the treatment period compared to the pretreatment period (mean: -58 +/- 15%) and recovered the pretreatment consumption in the posttreatment period, without significant changes in the consumption of food and/or total water. The only significant change observed in UChA rats was a decrease of the consumption of solid food (mean: -15 +/- 5%). Results are consistent with the idea that a dopaminergic D2 synapsis participates in the neural network responsible for satiation with ethanol.
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