C. Timo-Iaria

Phases and states of sleep in the rat

Abstract The sleep of 60 Wistar albino rats was studied with chronically implanted electrodes to record the electrocorticogram (ECoG), the cervical electromyogram, and eye movements. The ECoG changes in areas 10, 4, 6, 1, 2, 2a, 3 and 7 paralleled the patterns found in the human EEG during the various stages of sleep, whereas in areas 23, 24, 29b, and 29c the waves were in synchronism with the dorsal hippocampus, thus allowing to follow the limbic electrical activity during sleep. The desynchronization of arousal was found distinct from the pattern recorded during the paradoxical phase. It is suggested that what is termed slow-wave or synchronized sleep, and paradoxical phase or desynchronized sleep be considered, respectively, synchronized and desynchronized states of sleep, each one comprising more than one phase or stage.

Influence of environmental temperature on the sleep-wakefulness cycle in the rat ☆

Abstract The changes underwent by the sleep-wakefulness cycle were studied in 46 Wistar albino rats, separated as three groups which were adapted to 14°, 24° and 30°C and there-after observed under several conditions of steady or varying temperature. A strong and complex influence of the environmental thermal conditions was demonstrated. Paradoxical sleep is reduced at low and very high temperatures whereas arousal increases. Arousal and synchronized sleep are affected by the rate of temperature variation and desynchronized sleep is affected only by the direction of variation. Previous adaptation shifts the range of sleep as a function of the adaptation temperature but also of the actual thermal level. A correlation between control of the sleep-wakefulness cycle and thermoregulation is discussed.

Neural systems responsible for the gastric secretion provoked by 2‐deoxy‐D‐glucose cytoglucopoenia.

1. The central structures responsible for the gastrosecretory effect of cytoglucopoenia caused by 2‐deoxy‐D‐glucose (2‐DG) were investigated in 105 cats prepared with chronic gastric fistulae and subjected to various experimental procedures. 2. Bilateral electrolytic lesion of the caudalmost two thirds of globus pallidus almost suppressed the secretory response and caused aphagia and adipsia. 3. Secretion in response to 2‐DG and feeding behaviour were entirely blocked after making a lesion in a large ventromedial area of the meso diencephalic transition comprising the ventral tegmental area of Tsai, the ventral tegmental decussation, the red nucleus, a ventral portion of the central grey matter, the interstitial nuclei of Darkschewitsch and of Cajal, the pre‐rubral fields, the reticular part of substantia nigra, the internal portion of the cerebral peduncle and the ventral part of the mesencephalic reticular formation. 4. Microinjection of 2‐DG in the medial forebrain bundle, at the level of the hypothalamus, caused intense gastric secretion, whereas the same procedure was totally ineffective when the caudalmost two thirds of the globus pallidus were stimulated. 5. Increasing doses of 2‐DG, systemically injected, restored the secretory response in volume and acid concentration and output after intercollicular transection of the brain stem. After the transection, secretion of pepsin was only slightly increased when large doses of 2‐DG were administered, thus suggesting a differential control of water, acid and pepsin secretion in response to cytoglucopoenia. 6. It is concluded that there are at least three reflex systems involved in gastric secretion due to cytoglucopoenia: (a) a reflex consisting of afferent and efferent pathways in the medial forebrain bundle area; (b) a reflex whose afferent side is from the hypothalamus and efferent side is from the globus pallidus; (c) a reflex with the afferent side probably originating in the liver and the efferent side in the lower brain stem. 7. The pathways involved in the first two arcs run along Nautas limbic mid‐brain circuit. The three systems are possibly related to control of secretion and feeding behaviour.

Metabolic consequences of food restriction in rats

Abstract Some aspects of carbohydrate metabolism were studied in rats subjected to food restriction (single daily meal offered during two hours, either diurnal or nocturnal) for a week. Nocturnal preference for the nocturnal meal was patent in spite of food restriction, inasmuch as the rats fed from 8:00 to 10:00 p.m. ingested significantly more than those fed from 8:00 to 10:00 a.m. The amount of food ingested by rats of both groups was lower than that ingested by the animals with free access to food (as evaluated in 24 hours); nevertheless, both food-restricted groups did not lose weight for the duration of the experiments. The more prominent carbohydrate metabolic adaptations to food-restriction were: (1) high hepatic glycogen concentration during the intermeal periods; (2) hyperglycemia in the 12, 14 and 16 hour intermeal periods; (3) insulinemia was lower than in rats having free access to food all day long; (4) gastric emptying was delayed.

Metabolic performance of free fed rats subjected to prolonged fast as compared to the metabolic pattern in rats under long term food restriction

Glycemia, free fatty acids, insulinemia, hepatic glycogen, adrenal ascorbic acid, the amount of food ingested and of feces eliminated, gastric emptying and body weight were measured in two groups of rats of the same age. The F, free fed group was subjected to fast during 22 hours and then had a final meal for two hours. The R rats, subjected to food restriction from one to four weeks, had also a final two hour meal after the regular period of 22 hours with no access to food, and then both groups were treated equally. Coincidently, gastric emptying was more delayed, liver glycogen concentration was highest and glycemia was better maintained in the R than the F rats, particularly after three and four weeks of training. Probably due to their greater dependence upon the more frequent supply of nutrients, the F group had a larger free fatty acids mobilization during fast. Adrenal hyperactivity was induced in both groups and the amount of food ingested progressively increased in the R group and decreased in the F group. In general the metabolic efficiency tended to converge to a similar order of magnitude in both groups of animals by the end of the third week. A delayed gastric emptying seems to be a major factor in the adaptations to food restriction.

Site of action of 2‐deoxy‐D‐glucose mediating gastric secretion in the cat

1. Site of action of 2‐deoxy‐ D‐glucose (2‐DG) responsible for its effect on gastric secretion was investigated in cats prepared with polyethylene or nylon cannulae chronically implanted in the antrum.

Changes of carbohydrate metabolism caused by food restriction, as detected by insulin administration ☆

Abstract Metabolic changes induced in the rat by food restriction were assessed by administration of insulin (0.025 U/kg BW). The animals subjected to a 2 hr feeding/22 hr fasting schedule during one week have a greater capacity to recover from hypoglycemia even after 4 and 8 hr of fasting, whereas those with free access to food have a far lesser capacity to recover. Food restriction also caused a greater resistance to hepatic glycogen depletion during the hypoglycemic phase. It is likely that the metabolic adaptation during food restriction is important for glucose homeostasis and for rapid mobilization of energetic substrate during prolonged fasting.

Decreased blood pressure due to brain septal stimulation: Parameters of stimulation, bradycardia, baroreceptor reflex

Abstract Effects of varying the pulse length, frequency and duration of the electrical stimulus applied to the septal area of the chloralosed cat were studied. The degree of the blood pressure fall was taken as an index of the efficiency of the stimulation. Unidirectional pulses of 0.1,1,5,10, and 15 msec were tested. Pulse duration of 10 msec was generally the most effective. Frequencies of 15–50 and 80 cps were used, the frequency of 50 c/s was the most efficient. Stimulation time prolonged to 28.5 min showed that the septal area is very resistant to fatigue. Bradycardia was also studied and it was observed that eserine enhance the bradycardic effect of septal stimulation. Sometimes bradycardia was still present after vagotomy thus suggesting a diminution of cardiac sympathetic tone. The baroreceptor reflex was blocked by the hypotension due to septal stimulation; the possibility is advanced of a partial inhibition of the bulbar vasomotor center by impulses originating in the septal area.

Increase of food intake induced by glucagon in the rat

The effect of intraperitoneal administration of saline, glucose (25 mg/100 g b.w.), insulin (0.025 U/100 g b.w.) and glucagon (50 micrograms/kg b.w.) on glycemia, liver glycogen concentration and food intake was studied on 104 male adult Wistar rats. When saline was injected the amount of food ingested was similar to that expected at the metabolic moment selected for the tests. Glucose administration did not reduce food intake but both insulin and glucagon provoked a threefold increase during the 60 minutes ensuing the injection. The overall ingestion of food during the 24 hours after the injection of the hormones was significantly higher (about 10%) than the control values during the preceding or the succeeding 24 hours. A hyperphagic, rather than a hypophagic effect of glucagon administration is possibly related to the small dose used in the experiments. The mechanisms involved in the increase of food intake due to glucagon are discussed in terms of acceleration of the metabolic reactions that normally prevent large drops of glycemia as glucose utilization proceeds during the inter-meal periods and that in physiological conditions build up until the need for food arises.

Absence-like seizures in adult rats following pilocarpine-induced status epilepticus early in life

Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE) is induced at an early age. To determine in detail the electrophysiological patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17 days old, were subjected to SE induced by pilocarpine and electro-oscillograms from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120 days later. Six control animals of the same age range did not show any signs of epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1 0.5 Hz in frequency, 18.9 9.1 s in duration) were recorded from the frontal cortex during absence fits. However, similar spike-wave discharges were always found also in the hippocampus and, less frequently, in the amygdala and in thalamic nuclei. Repetitive or single spikes were also detected in these same central structures. Clonic movements and single jerks were recorded from all the rats, either concomitantly with or independently of the spike-wave complexes and spikes. We conclude that rats made epileptic with pilocarpine develop absence seizures also occurring during paradoxical sleep, showing the characteristic spike-wave bursts in neocortical areas and also in the hippocampus. This is in contrast to the well-accepted statement that one of the main characteristics of absence-like fits in the rat is that spike-wave discharges are never recorded from the hippocampal fields.