Comparative effects of developmental thiamine deficiencies and ethanol exposure on the morphometry of the CA3 pyramidal cells.

Maternal alcoholism and thiamine deficiency are frequently considered to be the causal agents of the central nervous system (CNS) damage associated with mental retardation in the offspring. For further understanding of pathological mechanisms underlying CNS damage in both disorders, histological studies were undertaken in developing rats to compare the hippocampus CA3 pyramidal cells measurements and density between three patterns of thiamine deficiency and chronic alcohol exposure. Female rats were given thiamine-deficient diet during different periods of gestation and lactation to obtain pre-, peri-, and postnatal thiamine-deficient pups. Twelve percent ethanol/water drinking fluid was given to mothers throughout gestation and lactation to obtain ethanol-exposed pups. Thiamine was administered during developmental ethanol exposure to assess the extent of interference between ethanol and thiamine metabolism. Nondrug-treated dams were allowed ad lib access to food and water during gestation and lactation to yield control pups. Hippocampus histology was performed in 45-day-old rats, and the CA3 pyramidal cells measurements and density assessed and compared between all treatment groups. It appears that the mean nuclear size of pyramidal cells in the field CA3 was significantly reduced in all the treatments compared to the control. While the mean nuclear size decreased more severely in development ethanol exposure than in the three patterns of thiamine deficiency, no significant difference was noted when pre-, peri-, and postnatal thiamine-deficient rats were compared. However, thiamine administration during developmental ethanol exposure partially restored the mean nuclear size. In contrast, comparisons between ethanol-exposed pups and the three patterns of thiamine-deficient pups, exhibited similar intensity in the deficit of CA3 pyramidal cells. Cell loss generated by ethanol treatment was not suppressed by thiamine administration. Common and separate mechanisms underlying the effects of alcohol intoxication and thiamine deficiency on cell death and cell atrophy were suggested.

Study of the 5-HT2 antagonist ritanserin on sleep-walking cycle in the rat.

Ritanserin, a 5-HT2 receptor antagonist, was injected intraperitoneally to rats at light onset. It was found that 0.63 mg/kg decreased waking, increased the slow waves characteristic of the first stage of sleep, and decreased paradoxical sleep (PS) during the first four hours. Active waking was further decreased and slow wave stage increased during the following four hours. The number of synchronized and paradoxical sleep phases decreased whereas their duration increased during the first four hours. Ritanserin at 2.5 mg/kg decreased active waking and PS, whereas quite waking and slow wave stage were increased during the first four hours. Quiet waking was increased during the following four hours. It is concluded that serotonin acting on 5 HT2 receptors is actively involved in sleep-waking regulation.

The intermediate stage of sleep in mice.

Seven mice of Balb/C strain were implanted with electrodes to perform sleep-waking recordings. In 100% of the cases, the mice showed, prior to paradoxical sleep, the intermediate stage of sleep characterized by high-amplitude cortical spindles interspersed with slow waves and low-frequency theta rhythm in the dorsal hippocampus. Consequently, the intermediate stage which seems to correspond to a transient functional isolated forebrain does exist in the rat, cat and mouse. in the rat, cat and mouse.

Hippocampal and cortical EEG activity in rats with transected hypothalamus.

The brain was transected in eight rats: the transection passed through the posterior pole of the superior colliculi and ended down at midhypothalamic level. The EEG activity in the dorsal hippocampus and cortex showed continuously slow, high amplitude waves. Thus the posterior hypothalamus is critical for the previously described hippocampal theta rhythm found in rats transected at the posthypothalamic level.

Automatic sleep-wake scoring in the rat on microcomputer APPLE II.

An automatic scoring system in real time of sleep-wake behavior in the rat was elaborated on microcomputer APPLE II. Four electrophysiological recording channels were used to distinguish seven behavioral states. Because the rat shows behavioral stages which are short-lasting, the analysis is performed second by second. It is based on the detection of the signal energy in specific frequency bands. The percentage of time passed in each stage is computed every 15 min, 1 h, 6 h and 24 h, the analysis extending during several days without interruption. The data are also printed out in a listing in real time and histograms in batch mode. Because of the interindividual differences, a calibration is needed. It is performed with a program in batch mode which allows an adjustment of parameters of determination from given specific digitized sequence in each rat. The accuracy of the automatic method was tested by the C contingency test, the theoretical maximal level being at 0.93: the intra- and inter-researchers contingency was 0.89, that between researchers and the computer was 0.85.

Fetal serotoninergic transplants in the fourth ventricle of adult rodents reverse sleep disturbances induced by neonatal administration of 5,7-dihydroxytryptamine.

Rats received a neonatal (at 4 days of age) intracisternal injection of 5,7-dihydroxytryptamine which eliminates serotonin (5-HT) throughout adulthood. Sleep recordings, performed on these rats at adult age, demonstrated significant decreases in paradoxical sleep. Dissociated fetal 5-HT cell suspensions transplanted in the IVth ventricle of these rats restored paradoxical sleep. However, fetal neuronal noradrenergic or cholinergic transplants did not restore paradoxical sleep. These results suggest that paradoxical sleep is directly or indirectly mediated through serotoninergic mechanisms.

[Neonatal administration of 5,7-dihydroxytryptamine induces in the adult rat a decrease in paradoxical sleep restored by an intracisternal injection of fetal raphe cells]. / L'administration néonatale de 5,7-dihydroxytryptamine induit chez le rat adulte une chute du sommeil paradoxal, qui est restauré par l'injection intracisternale de cellules raphéennes foetales.

By a method of automatic on-line scoring of sleep-waking stages in the rat, a significant decrease of the mean circadian level of paradoxical sleep and a significant increase of light slow sleep were shown in adult animals after neonatal disruption of serotoninergic system by intracisternal injection of 100 micrograms of 5.7-dihydroxytryptamine, when compared to an aged matched sham group. The level of paradoxical sleep was restored in the neurotoxin-treated rats by an intracisternal injection of a suspension of foetal raphe neurons.

Cerveau isolé and pretrigeminal rat preparations.

Cortical and hippocampal EEG activity was analysed in cerveau isolé and and pretrigeminal rats. In the acute stage, waking EEG patterns were absent in the cerveau isolé, whereas sleep EGG patterns were absent in the preparations. However, already on the second day the EEG waking sleep cycle recovered in the majority of rats. Paradoxically, stimuli directed to the caudal part of the preparations evoked stronger cortical and hippocampal EEG arousal than olfactory and visual stimuli. The rats exhibited some locomotor and grooming behaviour and could be fed orally. It is concluded that the activity of the isolated cerebrum of the rat is similar to that of cat preparations, but that functions of the caudal neuraxis are superior in rats.

Study of sleep spindles in the rat: a new improvement.

The two kinds of sleep spindles, previously described in the rat, were studied in intact animals, cerveau isole preparations and unilaterally neodecorticated rats. The anterior (frontal) spindles reach their maximum during deep slow sleep, when accompanied by theta activity, during the so-called intermediate stage which occurs just before and after paradoxical sleep. This stage is extended by low doses of barbiturate and similar patterns are induced by an intercollicular transection. The anterior spindles are suppressed by unilateral nedecortication and become abortive on contralateral hemisphere. The posterior ones, larger when recorded in the dorsal hippocampus than an the occipital cortex precede the appearance of the theta activity of intermediate stage. They are absent when the theta rhythm is present, during the long-continued intermediate stage under barbiturate ad in the cerveau isole preparation; but an unilateral neodecortication does not prevent the occurrence of posterior spindles on the white matter. Thus, during deep slow sleep, the rat shows both frontal cortex spindles, fully spread out during intermediate stage, and posterior spindles, probably originating from structures implied in the theta genesis and heralding the occurrence of this rhythmic slow activity.

Cerveau isolé and pretrigeminal rats.

Cortical and hippocampal EEG activity was analysed in 14 cerveau isole and 8 pretrigerninal rats. In the acute stage, waking EEG patterns were absent in the cerveau isole, whereas sleep EEG patterns were absent in the pretrigeminal preparations. However, already on the second day the EEG waking-sleep cycle recovered in the majority of rats. Paradoxically, stimuli directed to the caudal part of preparations evoked stronger cortical and hippocampal EEG arousal than olfactory and visual stimuli. The behavior of the caudal part was observed in 25 preparations. Although in abortive form, the rats did show some locomotor and grooming behavior, and could be fed orally. The peripheral events of paradoxical sleep appeared only on the fourth or fifth day of survival of the cerveau isole rats. It is concluded that the activity of the isolated cerebrum of the rat is similar to that of cat preparations, but that functions of the caudal neuraxis are superior in rats.