Thyroid hormones modify susceptibility to lidocaine-kindling in rats.

Lidocaine, a local anesthetic, produces seizures by unknown central mechanisms. The objective of this study was to investigate the effect of cellular metabolism alteration, by changing thyroid hormones levels, on susceptibility to lidocaine-kindling. Lidocaine was administered daily (60 mg/Kg x day, i.p.) to rats treated with thyroxine (300 microg/Kg x day) or methimazole (60 mg/Kg day), dissolved in drinking water. After the 18th lidocaine administration, the cumulative percent of animals convulsed was higher (100%) for the methimazole-treated group and lower (20%) for the thyroxine-treated group, compared to the control group (40%). The results suggest that susceptibility to lidocaine-kindling depends on neuronal metabolism, which probably affects monoamines uptake mechanisms.

T3 deficiency prolongs convulsions induced by acute pentylenetetrazole.

The effects of 3,5,3'-triiodothyronine (T3) levels on threshold, latency and duration of pentylenetetrazole-induced seizures were tested in rats treated with thyroxine (300 micrograms/kg.day, N = 9) or methimazole (60 mg/kg.day, N = 5) dissolved in drinking water. Compared to controls (N = 7), methimazole treatment reduced T3 levels (45.4 +/- 2.0 vs. 33.0 +/- 4.8 ng/dl) and increased seizure duration (36.2 +/- 22.4 vs. 289.6 +/- 24.4 s) and threshold (29.0 +/- vs. 45.5 mg/kg). Thyroxine treatment increased T3 levels (45.4 +/- 2.0 vs. 67.7 +/- 4.8 ng/dl), but had no significant effect on seizures.

Convergence of gastric and hepatic information in brain stem neurons of the rat.

Convergence of gastric and hepatic information in the nucleus of the solitary tract (NTS) was investigated by single-pulse electrical stimulation of the hepatic and the gastric branches of the vagus. Facilitation induced by both stimuli occurred most often in responses of neurons in the NTS, indicating convergence of information there. In a second experiment using gastric distension and portal infusion of glucose to analyze such convergence, activation by gastric distension and suppression by portal glucose was the most prominent combination of responses to both stimuli. This confirmed the results of electrical stimulation, because distension increases the firing rate of gastric afferents and glucose infusion decreases the firing rate of hepatic afferents. Analysis of the responses to varying degrees of gastric distension revealed that some NTS neurons are activated by weak distension, but inhibited by strong distensions.

Dissociation of intake adjustments to sustained and day-to-day changes in food caloric density.

Rats were subjected to day-to-day changes in food caloric density superimposed on a sustained (average) change above or below the basal value. This was done by giving them a different diet every day, so that caloric density gradually increased from a basal value. By repeating this procedure the caloric density varied in a sinusoidal pattern above or below the basal value. Short-term compensatory changes in food intake followed a reversed and delayed sinusoidal pattern (compared to that of caloric density), and achieved only an incomplete compensation of caloric intake. On the other hand, long-term changes in the average food intake led to a complete compensation of the average caloric intake for the high-calorie diets. The low-calorie diets produced a marked body weight loss, although these rats maintained the partly compensatory responses to the day-to-day changes in caloric density; that is, food intake decreased when the caloric density of the diet increased to the basal value, overriding any effect of body weight loss. It is concluded that short-term and long-term controls of food intake are relatively independent of each other and that the short-term control determines the daily caloric intake, with a delay that probably indicates learning processes, while the long-term control is determining the average caloric intake over a period of several days, accounting for a more or less complete compensation of caloric density changes.

Ontogeny of alpha- and beta-adrenergic anorexia in rats.

The anorectic action of alpha- (phenylephrine) and beta- (isoproterenol) adrenergic agonists was studied in mildly deprived neonatal, weanling, prepubescent, and adult rats. Intraperitoneal phenylephrine produced a reduction of food intake at all ages but with reduced potency and with a maximum of 50% in neonates. Contrary to intramuscular epinephrine that has no effect on feeding at any age, intramuscular phenylephrine was as effective as intraperitoneal in neonates, probably because it is not as rapidly destroyed in tissues as epinephrine. However, in weanlings and adults intramuscular phenylephrine was much less anorectic than intraperitoneal, suggesting that this effect is exerted via the liver. Isoproterenol did not reduce milk intake at any age before adulthood. Lactate had no effect on milk intake before the age of 40 days. Thus catecholamine anorexia is a purely alpha-adrenergic effect in young rats and appears before the metabolic effect of lactate. beta-Adrenergic anorexia, on the other hand, can be obtained only after puberty, suggesting that the mechanism mediating it matures after the preparatory action of the sexual hormones.

Ontogeny of epinephrine-induced anorexia in rats.

Intraperitoneal or intraportal epinephrine elicits a strong inhibition of food intake in adult rats and dogs but has no effect when injected intramuscularly or intrajugularly, in spite of production of larger hyperglycemia and cardiovascular changes. These facts suggest that the effect of epinephrine on feeding is elicited via the liver. Ontogeny of this adrenergic control of food intake was studied in newborn and weanling rats. Anorexic effect of intraperitoneal epinephrine was clearly observed in dam-deprived 3-day-old neonatal rats (youngest in which it was tested), both when they were offered enriched milk through an anterior oral cannula while they were isolated from their dam and when they were allowed to suckle from her. However, anorectic effect was less in neonatal rats (day 3-13) than in adults. Weanling rats, 21-26 days old, were as sensitive to intraperitoneal epinephrine as adults. In 3- to 4-day-old rats it also reduced water intake, but this effect disappeared by day 12 and was not observed in mildly water-deprived adults. Peripheral adrenergic control of intake appears very early in ontogeny of rats. First, it affects food and water intake equally, but by day 12 it affects only food intake. Increase in sensitivity to epinephrine after weaning is probably due to an increase in number of hepatocytic adrenergic receptors and/or increase in enzymes necessary for hepatic effects of epinephrine.

Effect of adrenergic blockers and depleters on food intake in rats.

In rats kept at a constant temperature (24 +/- 1.5 degrees C) and on a reversed day/night cycle (light from 11 p.m. to 11 a.m.), the amount of food eaten during the first 2 h of darkness and during 24 h was measured every day. When reserpine or guanethidine were injected 5 min before the beginning of the dark period on four consecutive days, there was no significant change in the 0.5-, 1-, or 24-h food intake on the injection days, but there was a significant increase in the 0.5-, 1- and 2-h food intake during the next five to eight days, without any change in the 24-h intake. A single injection of dichloroisoproterenol produced no change on the day of injection but it induced a significant increase in the 0.5-, 1- and 2-h intake on the following 15 days, without any change in the 24-h intake. The increase in the early night-time feeding without any change in the 24-h intake was interpreted as an increase in meal size (diminished preabsorptive satiation) compensated by a decrease in meal frequency. Both reserpine and guanethidine are catecholamine depleters but the latter does not penetrate into the brain. Dichloroisoproterenol is a beta-blocker acting on the glycogenolytic effects of catecholamines. The results thus agree with the hypothesis that glycogenolysis elicited by the liberation of intrahepatic catecholamines from the sympathetic nerve endings and chromaffin cells plays a role in preabsorptive satiation.