Swiss battery-cage ban.
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Animal Husbandry↗
Biomedical subjects
A Steiger
Publications and source records attributed to A Steiger.
Bretazenil modulates sleep EEG and nocturnal hormone secretion in normal men.
Preclinical data suggest that the imidazodiazepinone derivative bretazenil (Ro 16-6028) has anxiolytic and anticonvulsant properties with only weak sedative effects. We examined the influence of oral administration of 1 mg bretazenil on the sleep EEG and the concomitant nocturnal secretion of cortisol, growth hormone and prolactin in ten healthy young men. After bretazenil we found a significant increase in stage 2 sleep and a significant reduction in stage 3 sleep. REM latency was prolonged. Spectral analysis of sleep-EEG power revealed a decrease in delta and in theta power and an increase in sigma power. We found no significant influence on sleep onset latency or on intermittent wakefulness. Bretazenil prompted a significant decrease in cortisol secretion and a significant increase in prolactin release. It had no major influence on growth hormone secretion.
Adult↗
The hypothalamic-pituitary-adrenocortical system and sleep in man.
This review article summarizes the major findings about the interactions of human sleep structure and the hypothalamo-pituitary-adrenocortical (HPA) system under physiological and pathophysiological conditions, including studies that probe the sleep effects of systemically administered HPA hormones. Human sleep is regulated by a concerted action of various signal compounds acting at sleep-generating neurons whose central organization is not yet fully understood. During nocturnal sleep the endocrine system is remarkably active, the longest established finding being that growth hormone (GH) release is associated with the initiation of sleep and that there is a steep morning rise of cortisol (Weitzman et al., 1966; Takahashi et al., 1968). Moreover, the effects of exogenously administered corticosteroids and of their excessive endogenous release (e.g. Cushing's disease) were recognized more than 20 years ago.
Adrenocorticotropic Hormone↗
DHEA administration increases rapid eye movement sleep and EEG power in the sigma frequency range.
Dehydroepi-androsterone (DHEA) exhibits various behavioral effects in mammals, at least one of which is enhancement of memory that appears to be mediated by an interaction with the gamma-aminobutyric acidA (GABAA) receptor complex. We investigated the effects of a single oral dose of DHEA (500 mg) on sleep stages, sleep stage-specific electroencephalogram (EEG) power spectra, and concurrent hormone secretion in 10 healthy young men. DHEA administration induced a significant (P < 0.05) increase in rapid eye movement (REM) sleep, whereas all other sleep variables remained unchanged compared with the placebo condition. Spectral analysis of five selected EEG bands revealed significantly (P < 0.05) enhanced EEG activity in the sigma frequency range during REM sleep in the first 2-h sleep period after DHEA administration. In contrast, the EEG power spectra of non-REM sleep were not affected, nor were the nocturnal time course curves of plasma cortisol, growth hormone, or testosterone concentration. The results suggest that DHEA administration has a mixed GABAA-agonistic/antagonistic effect, exerted either directly or through DHEA-induced changes in steroid metabolism. Because REM sleep has been implicated in memory storage, its augmentation in the present study suggests the potential clinical usefulness of DHEA in age-related dementia.
Adult↗
Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man.
The synthetic hexapeptide growth hormone-releasing peptide (GHRP-6) stimulates growth hormone (GH) release in animals and man. GH-releasing hormone (GHRH) has the same effect. In addition, pulsatile administration of GHRH in normal men results in increased slow-wave sleep (SWS) and blunted cortisol levels. The effect of GHRP on nocturnal hormone secretion and on the sleep electroencephalogram (EEG) is still unknown. We compared the effect of repetitive i.v. boluses (4 x 50 micrograms) of GHRP and placebo (PL) on the sleep EEG (23.00 to 07.00 h) and on the secretion profiles of GH, ACTH and cortisol (20.00 to 07.00 h) in normal male controls. After GHRP, the GH concentration (22.00 to 03.00 h) increased (15.4 +/- 9.6 ng/ml after GHRP vs. 5.5 +/- 4.0 ng/ml after PL, p < 0.02), as did the ACTH level (22.00 to 02.00 h: 21.0 +/- 5.3 pg/ml after GHRP vs. 16.6 +/- 3.1 pg/ml after PL, p < 0.02). During the total night, and particularly during the first half of the night, cortisol secretion was enhanced (22.00 to 03.00 h: 56.0 +/- 31.0 ng/ml after GHRP vs. 25.2 +/- 9.0 ng/ml after PL, p < 0.02). Stage 2 sleep increased (270.1 +/- 25.3 min after GHRP vs. 245.4 +/- 25.8 min after PL, p < 0.02), whereas other sleep-EEG variables including SWS remained unchanged. Our data demonstrate that GHRP stimulates not only GH release but also hypothalamic-pituitary-adrenocortical hormone secretion. The latter effect is opposite to the blunting of cortisol after GHRH. Both GHRP and GHRH promote sleep. However, GHRP enhances stage 2 sleep and does not affect SWS.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
[Sleep endocrinology].
Human sleep is characterized by the cyclic occurrence of episodes of non-REM and REM sleep and by distinct secretory patterns of several hormones. During depression and aging there are similar changes in the neurophysiological and the neuroendocrine components of sleep. A review of data deriving from clinical studies in patients and controls and from animal research supports the view of a bidirectional interaction between sleep structure and nocturnal hormone secretion. These data suggest that changes in the activity of neurohormones have a key role in the development of aberrant sleep during depression and during aging.
Adult↗
[Action of growth hormone releasing hormone (GHRH) on sleep EEG and nocturnal secretion of growth hormone, cortisol and ACTH in patients with major depression].
In contrast to the effects of GHRH in young normal human subjects, in which repetitive i.v. administration of GHRH prompts an increase in the amount of slow wave sleep (SWS) and in GH secretion and blunting of cortisol release, both in young and in old patients with depression there is no effect on SWS and cortisol release after GHRH, while GH secretion is stimulated. We assume that HPA activity and SWS are inert to the influence of GHRH during acute depression because of a slight CRH overactivity, whereas GHRH exerts effects on GH secretion.
Adrenocorticotropic Hormone↗
Reduction of plasma oxytocin levels in patients suffering from major depression.
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Adult↗
Flumazenil exerts intrinsic activity on sleep EEG and nocturnal hormone secretion in normal controls.
The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.
Adult↗
Effects of 5HT3 receptor antagonism by tropisetron on the sleep EEG and on nocturnal hormone secretion.
Two dosages (5 mg and 25 mg) of the selective 5HT3 receptor antagonist tropisetron (ICS 205-930) were administered to healthy male controls, and the effects on the sleep EEG and nocturnal secretory activity of growth hormone (GH) and cortisol were evaluated. The lower dosage was administered to four subjects and the higher dosage to eight on 5 consecutive days, preceded and followed by 2 days of placebo treatment. After 25 mg of tropisetron, there was a slight increase in REM sleep in the first part of the sleep period, and stage 2 was decreased during the total night. In addition, plasma cortisol levels increased earlier than under placebo, and plasma GH levels were reduced in the second part of the night. Thus, only discrete effects of tropisetron upon sleep-endocrine activity were noted, making it unlikely that serotoninergic neurotransmission exerts its well-documented effects upon sleep through 5HT3 receptors.
Adult↗
Effects of long-term treatment with the MAO-A inhibitor moclobemide on sleep EEG and nocturnal hormonal secretion in normal men.
Sleep EEG, nocturnal penile tumescence (NPT) and nocturnal hormone secretion were studied in four normal males during placebo, under up to 300 mg per day of moclobemide, the short-acting and reversible inhibitor of monoamine oxidase (type A), and after withdrawal. Under moclobemide, REM sleep was slightly suppressed. Drug cessation was followed by REM rebound. In contrast to REM sleep, NPT was not affected by the drug. The nocturnal cortisol concentration was elevated under moclobemide and this effect persisted after withdrawal. No influences on growth hormone, prolactin, testosterone, luteinizing hormone or follicle-stimulating hormone were found.
Adult↗
Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation.
The steroid pregnenolone (P) and its sulfate (PS) can accumulate in the central nervous system independent of peripheral sources. Pharmacologically, the sulphated form of P interacts with the GABAA receptor complex, and functional assays show that this steroid behaves as an allosteric GABAA receptor antagonist. The present study explored the effect of a single dose of P upon the sleep-EEG and concurrent secretion of growth hormone and cortisol in male volunteers. P increased the amount of time spent in slow wave sleep and depressed EEG sigma power. Sleep-associated nocturnal cortisol and growth hormone secretion remained unchanged, ruling out the possibility that P exerted its effect via altered regulation of these hormones. Furthermore, results from in vitro studies on the potency of P to activate gene transcription via corticosteroid receptors made a genomic action of P via hormone receptor-sensitive DNA sequences unlikely. We conclude that P acts in a non-genomic fashion at or in the vicinity of the benzodiazepine binding site, modulating allosterically the GABAA receptor like a partial inverse.
Adult↗
The sleep EEG and nocturnal hormonal secretion studies on changes during the course of depression and on effects of CNS-active drugs.
1. The sleep EEG and nocturnal hormone secretion were studied simultaneously in normal male controls and in male patients with major endogenous depression before treatment with tricyclics and after recovery and drug cessation. 2. Several studies were performed in normal male controls to investigate the effect of antidepressants (brofaromine, moclobemide, amitriptyline, clomipramine and trimipramine) and of neuropeptides (CRH and the ACTH (4-9) fragment analog ebiratide) on the sleep EEG and sleep-associated hormone secretion. 3. Elevated cortisol and blunted testosterone secretion are state markers of acute depression, whereas sleep EEG, GH and prolactin variables do not show marked differences between acute depression and recovery. Except for trimipramine, all antidepressants investigated suppress REM sleep. No systematic relationship between the sleep EEG and endocrine effects of antidepressants is detectable. Pulsatile application of CRH in controls mimicks some of the neurobiological symptoms of acute depression. More shallow sleep occurs under ebiratide, whereas hormonal secretion remains unchanged. 4. Our data demonstrate that antidepressants exert distinct effects on sleep. However, these substances do not induce changes in sleep structure which persist after their withdrawal in remitted patients. Pulsatile application of neuropeptides leads to specific effects on CNS activity which are not mediated by changes of peripheral hormone secretion. The view that CRH plays a key role in the pathophysiology of affective disorders is corroborated.
Adult↗
Differential effects of the enantiomers R(-) and S(+) oxaprotiline on major endogenous depression, the sleep EEG and neuroendocrine secretion: studies on depressed patients and normal controls.
The effects of the optically active enantiomers of oxaprotiline (OXP), R(-) OXP and S(+) OXP, on depressive symptomatology and the sleep EEG were investigated in two separate exploratory studies. In addition, the neuroendocrine profile of both compounds was characterized in normal controls. In the patients treated with a daily oral dose of 150 mg S(+) OXP we found a Hamilton depression score that decreased from 29.1 +/- 1.8 (SEM) on day 0 to 14.7 +/- 3.2 on day 28 (P < 0.01). Six patients were judged to be full responders (HAMD score 0-7 points), three were improved (HAMD score 8-15) and four were nonresponders (HAMD score > 16). The therapeutic effect achieved with 150 mg R(-) OXP daily was less pronounced: the HAMD score decreased from 27.8 +/- 2.5 on day 0 to 19.4 +/- 3.2 on day 28 (P < 0.05). There were two full responders, one improved patient and seven nonresponders. The sleep EEG scoring revealed a marked suppression of REM sleep among patients treated with S(+) OXP but not with R(-) OXP. In the normal controls, a single oral dose of 75 mg S(+) OXP prompted an increase in the secretion of cortisol and growth hormone, whereas 75 mg R(-) OXP did not. Neither enantiomer influenced the secretion of testosterone or prolactin.
Adult↗
Studies of nocturnal penile tumescence and sleep electroencephalogram in patients with major depression and in normal controls.
Nocturnal penile tumescence (NPT), sleep electroencephalogram and testosterone secretion were investigated in 25 nonmedicated male patients with an acute episode of major depression. Twelve patients were reassessed after a stable remission and withdrawal of antidepressants. Four of the 25 patients had no NPT activity during acute depression, but this was reversed after recovery. The area under the NPT curve increased after remission, whereas all other NPT variables remained unchanged. Nocturnal testosterone secretion was enhanced after recovery, whereas the sleep structure remained unchanged. The NPT findings for the depressed patients did not differ from those for a control group, even though the latter group was younger. Hence, there are no general NPT changes that could be used to separate depressed patients and normal controls. However, a lack of NPT seems to be a possible, reversible symptom of depression in men.
Adult↗
Sleep EEG effects of 3,4-methylenedioxyethamphetamine (MDE; "eve") in healthy volunteers.
3,4-methylenedioxyethamphetamine (MDE; "Eve") exerts similar psychotropic effects in humans as 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and is less toxic in animal studies. We conducted a double-blind, placebo-controlled, cross-over sleep electroencephalogram (EEG) study with healthy volunteers. One hundred forty milligrams of MDE or placebo were administered PO in six subjects at 11 PM. Sleep EEG was registered from 11 PM-7 AM the next morning. All subjects had a normal sleep onset latency. They all awoke 60 to 120 min after administration of MDE and stayed awake for at least 150 min (total sleep time, TST MDE < placebo and intermittent time awake MDE > placebo: p < 0.001). After again falling asleep rapid eye movement (REM) sleep was totally suppressed (REM during time in bed, TIB MDE < placebo: p < 0.001). A cyclic alternation of relatively long periods of slow wave sleep (SWS) with periods of light sleep occurred in three subjects during the second part of the night (stage 4 in second part of night MDE > placebo: p = 0.16). The effects of MDE on sleep variables largely demonstrate the stimulant, amphetamine-like properties of MDE.
3,4-Methylenedioxyamphetamine↗
Studies on geranylgeranyl diphosphate synthase from rat liver: specific inhibition by 3-azageranylgeranyl diphosphate.
Geranylgeranyl diphosphate synthase from rat liver was separated from farnesyl diphosphate synthase, the most abundant and widely occurring prenyltransferase, by DEAE-Toyopearl column chromatography. The enzyme catalyzed the formation of E,E,E-geranylgeranyl diphosphate (V) from isopentenyl diphosphate (II) and dimethylallyl diphosphate (I), geranyl diphosphate (III), or farnesyl diphosphate (IV) with relative velocities of 0.09:0.15:1. 3-Azageranylgeranyl diphosphate (VII), designed as a transition-state analog for the geranylgeranyl diphosphate synthase reaction, was synthesized and found to act as a specific inhibitor for this synthase, but not for farnesyl diphosphate synthase. Diphosphate V and its Z,E,E-isomer (VI) also inhibited geranylgeranyl diphosphate synthase, but the effect was not as striking as that of the aza analog VII. Specific inhibition of geranylgeranyl diphosphate synthase by VII was also observed in experiments with 100,000g supernatants of rat brain and liver homogenates which contained isopentenyl diphosphate isomerase and prenyltransferases including farnesyl diphosphate synthase as well as geranylgeranyl diphosphate synthase. For farnesyl:protein transferase from rat brain, however, the aza compound did not show a stronger inhibitory effect than E,E,E-geranylgeranyl diphosphate.
Animals↗
Effects of corticosteroids and neurosteroids on sleep EEG.
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Adrenal Cortex Hormones↗