Increase In Slow Wave Activity Research Articles

Long-term effects of thyroid hormone deficiency on noradrenergic circuitry: electrophysiological changes in intraocular hippocampus–locus coeruleus double transplants

The effects of thyroid hormone deficiency on the noradrenergic innervation of hippocampus from locus coeruleus (LC) were examined using intraocular double transplants in albino rats. Fetal brainstem pieces containing the nucleus LC were transplanted to the anterior chamber of the eye of thyroidectomized and normal recipients and the brain grafts were allowed to mature for 8 weeks. Pieces of fetal hippocampal formation were introduced into the anterior eye chamber and placed in contact with the LC grafts or placed in previously operated eyes. As evidenced by high performance liquid chromatography, hippocampal transplants in contact with a brainstem graft gradually became hyperinnervated by noradrenergic fibers from these grafts. The levels of norepinephrine were lower in single control grafts and in double grafts in thyroidectomized animals than in control double grafts. Extracellular recordings of single neuronal activity were performed in hippocampal transplants in all 3 groups after 10-14 months in oculo. Superfusion with the α2- adrenergic agonist clonidine and the α-adrenergic antagonist phentolamine elicited significant increases in discharge rate of hippocampal neurons in control double transplants, but not in single hippocampal grafts or in double grafts in thyroidectomized hosts. The β-adrenergic antagonist timolol did not change the neuronal firing rate in any of the 3 groups. Superfusion with penicillin over single hippocampal transplants caused long-lasting increases in slow-wave activity. This increased bioelectric activity remained after the cessation of drug application. A similar increase in slow-wave activity was found in hyperinnervated control double transplants only when penicillin was combined with clonidine or phentolamine. However, the hippocampal portion of double grafts in thyroidectomized recipients readily responded to penicillin with seizures and/or interictal spiking. The data presented here suggest that chronic lack of thyroid hormones leads to significant disturbances of the central noradrenergic transmission in isolated LC-hippocampal circuits.

Effects of acute and chronic treatment with an atypical antidepressant drug, nomifensine, on the sleep-wake activity in rats.

After the chronic administration of saline, rats were treated with nomifensine (0.1 or 1.0 mg/kg, twice a day, at light and dark onset) for 11 days. The sleep-wake activity was recorded for 24 h on the baseline day (saline), on nomifensine days 1, 5 and 11, and also on day 12, when saline was injected again (withdrawal day). Another group of rats was treated with saline throughout the experiment, without significant effect on the sleep-wake activity. The smaller dose of nomifensine increased non-REM sleep (NREMS) at the expense of wakefulness (W) in the light period. The effect persisted throughout the chronic treatment. A late increase in REM sleep (REMS) was noted on nomifensine days 5 and 11. Nomifensine failed to affect the sleep-wake activity in the dark period. On withdrawal, the baseline percentages of the vigilance states were recovered. As evaluated through spectral analysis of the EEG, the increase in NREMS was accompanied by an increase in slow wave activity. The higher dose of nomifensine elicited an increase in W and a reduction in both sleep states, followed by changes in W and NREMS in the opposite directions. These effects were evident in both the light and the dark periods of the day. Chronic treatment resulted in circadian variations in the effects. Withdrawal of the drug abolished the arousal reaction, but the late increase in NREMS persisted. The dose-dependent biphasic effects of nomifensine on sleep-wake activity can be explained by considering the proposed indirect dopamine and possibly noradrenaline agonist activity of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of sleep deprivation on sleep and EEG power spectra in the rat

EEG power spectra of the rat were computed for consecutive 4-s epochs of the daily light period and matched with the scores of the vigilance states. Sleep was characterized by a progressive decline of low frequency spectral values (i.e. slow wave activity) in non-rapid eye movement (non-REM) sleep, and a progressive increase in the amount of REM sleep. During recovery from 24-h total sleep deprivation (TSD) the following changes were observed: an increase of slow wave activity in non REM sleep with a persisting declining trend; an enhancement of theta activity (7.25-10.0 Hz) both in REM sleep and waking; a decrease of non-REM sleep and an increase of REM sleep. In addition, a slow wave EEG pattern prevailed in the awake and behaving animal during the initial recovery period. In selective sleep deprivation paradigms, either REM sleep or slow wave activity in non-REM sleep was prevented during a 2-h period following upon 24-h TSD. During both procedures, non-REM sleep spectra in the lowest frequency band showed no increase. There was no evidence for a further enhancement of slow wave activity after its selective deprivation. The results indicate that: (1) slow wave activity in non-REM sleep and theta activity in REM sleep may reflect sleep intensity; and (2) REM sleep and active waking, the two states with dominant theta activity, may be functionally related.

275 DEVELOPMENT OF SMALL BOWEL MOTILITY IN BEAGLE PUPPIES

To investigate the neonatal development of upper small bowel (SB) peristalsis and the effect of pentagastrin (PG) on motility, we monitored duodenal intraluminal pressure manometrically in 11 beagle puppies from birth until weaning at 5 wk. The response rate of the system employed was 150 mm Hg/sec. Electrodes were implanted on the SB serosal surface for subsequent monitoring of myoelectric activity during the first 2 mo. in 3 add'l puppies. During the first 3 wk there was an increase in duodenal contraction rate immediately after a liquid meal from 11±0.4/min to 16±1/min (p <0.001) followed by a slight decrease during weaning. Peak duodenal pressure increased from 17 to 38 mm Hg (p < 0.002), and subsequently decreased to 25 mm Hg with weaning. The duration of each contraction shortened during the first 3 wk from 3.4 to 2.4 sec (p <0.001). Myoelectric monitoring revealed a gradual increase in slow wave activity from 14 to 20 cycles/min in both fasting and fed states, corresponding with the increased contractions observed in the manometric studies. These developmental changes are similar to those which occur in the beagle lower esophageal sphincter (LES) and stomach during suckling and weaning. However, in contrast to the lack of sensitivity to PG by the beagle LES and stomach during the first week, SB contractions were inhibited on day 1 with 0.03-8 ug/kg PG s.c. We speculate that the differential PG sensitivity of LES, stomach, and SB during the first week of life in the beagle is due to differential gastrin receptor number and/or affinity.

THE ACTIONS OF DIHYDROXYPHENYLALANINE AND DIHYDROXYPHENYLSERINE ON THE SLEEP‐WAKEFULNESS CYCLE OF THE RAT AFTER PERIPHERAL DECARBOXYLASE INHIBITION

1. The actions of dihydroxyphenylalanine (DOPA) and dihydroxyphenylserine (DOPS) were assessed on the sleep-wakefulness cycle of male Wistar rats. 2. In comparative studies the extracerebral decarboxylase was inhibited with serinetrihydroxybenzylhydrazide (RO 4-4602) before injection of DOPA or DOPS. 3. DOPA (80-160 mg/kg, i.p.) with or without previous inhibition of the peripheral decarboxylase gave rise to an initial significant increase of slow wave activity, which may be related to a release of 5-hydroxytryptamine. 4. During the subsequent 8 h sessions, DOPA significantly decreased slow wave sleep and rapid eye movement sleep (REM) and increased wakefulness. 5. DOPS (80-160 mg/kg, i.p.) did not significantly modify the sleep-wakefulness cycle apart from a decrease of the latency for the first REM episode after 160 mg/kg in the RO 4-4602 pretreated animals.

Human sleep and EEG through a cycle of methadone dependence

The effects of oral methadone on EEG and sleep were studied in 6 male postaddicts. Continuous nocturnal measurement of EEG, EMG and EOG was used to define sleep patterns. Period analysis and power spectral analysis were performed on each 8 min sample of daytime (eyes closed) EEG. Both sleep and EEG were studied during a predrug control period, during the methadone induction phase (45–60 mg/day), stabilization phase (100 mg/day), and then 6, 10, 13, 18 and 22 weeks after withdrawal. One subject did not complete the last two withdrawal sessions. While on methadone, subjects reported that they slept more and also showed an increase in slow wave activity and a decrease in fast wave activity of their EEG during this time. Nocturnal sleep was not markedly altered during the chronic administration of methadone. Subjects reported an increase in dreaming soon after withdrawal, and then 3–5 weeks of nocturnal insomnia. At the 6th week after withdrawal, slow wave activity in the daytime EEG was decreased, fast wave activity was increased, and mean EEG frequency was increased. REM sleep and delta sleep were increased during withdrawal. These data provide further evidence that chronic administration of narcotic analgesics may induce persistent functional changes in the central nervous system.

Effects of antidepressant drugs on wakefulness and sleep in the cat

Wakefulness-sleep cycles were determined for each 24 hour period during control days and each day following the administration of various antidepressant agents; i.e., amitriptyline, desmethylimipramine and imipramine; chlorpromazine and perphenazine; pargyline; or methamphetamine. All of the agents induced an initial suppression of RPS. Methamphetamine induced an increase in total wakefulness during the suppression, whereas the other agents studied induced an increase in slow wave activity during the suppression. None of the agents induced a clear RPS rebound. The normal wake-sleep cycle reappeared in 3–4 days following the tricyclics and phenothiazines, in 4–5 days following pargyline, and in 2 days following methamphetamine.