The present two experiments were designed to investigate the effects of a synthetic and of a natural corticosteroid on nocturnal sleep in humans. Both experiments were held double-blind and designed according to a within-subject cross-over comparison. In the first experiment, 1 mg of dexamethasone applied orally prior to sleep (11.00 p.m.) led to a reduction of the percent of time spent in REM and in stage 4 sleep. The amount of stage 2 sleep tended to be increased after dexamethasone. In the second experiment, an infusion of 100 mg hydrocortisone throughout the night also reduced REM, but increased stage 4 sleep. A statistical comparison of both experiments suggested that both steroids not only reduced REM sleep but also tended to enhance intermittent wakefulness. This analysis also confirmed opposite effects on measures of slow-wave sleep of both substances. The results represent a first demonstration of differential effects of synthetic and natural corticosteroids on sleep, which has to be substantiated in further studies directly comparing effects of these steroids.
We investigated effects of bolus administration of corticotropin-releasing factor (CRF) on parameters of cardiac activity in isolated working rat hearts. Effects at a dose of 5 micrograms of CRF were compared in hearts perfused with Krebs-Henseleit solution, norepinephrine (NE, 10(-9) M), propranolol (3 x 10(-6) M), NG-nitro-L-arginine (L-NNA, 3 x 10(-5) M), or indomethacin (3 x 10(-5) M). CRF increased coronary flow for > 30 min (P < 0.01) with maximum increases of 31.7%, suggesting a prolonged vasodilatory action of the peptide. CRF, in addition, induced transient (lasting < 10 min) increases in maximum aortic pressure and oxygen consumption (P < 0.01), suggesting an inotropic action of the peptide. Perfusions of NE and propranolol did not change the cardiac response to CRF. L-NNA, inhibiting release of endothelium-derived relaxant factor (EDRF), and indomethacin diminished the vasodilatory response to CRF, as indicated by significantly shortened increases in coronary flow after CRF (P < 0.05). Indomethacin also enhanced peak increases in maximum aortic pressure after CRF (P < 0.01). The data confirm direct effects of CRF on cardiac activity. They also suggest that the mediation of coronary vasodilation by CRF involves the endothelial release of prostacyclin and EDRF.
The present study was designed to investigate effects of cortisol on evoked potential indicators of sensory processing and on mood in 45 healthy human subjects. In order to determine the glucocorticoid effect to be primary excitatory or inhibitory, the vertex potential components (PI, Nl, P2) of the auditory evoked potential (AEP) were assessed, which also indicate a stimulus-induced cortical arousal response mediated by the nonspecific sensory system of the reticular formation. The AEPs were recorded while the subject performed a vigilance task containing 8 blocks of monotonous series of tone pips presented at different interstimulus intervals. Mood was assessed by an extensive adjective checklist. Experiments were held double-blind and designed as between-group comparison. Subjects received either 40 or 20 mg hydrocortisone (constantly infused between 35 min prior to testing till the end of the experiment), or placebo. Enhanced plasma cortisol levels were related to increased amplitudes of the AEP vertex response. Furthermore, cortisol augmented self-reported concentration and reduced tiredness during task performance. The glucocorticoid effects on both AEPs and self-report measures suggest an excitatory influence of cortisol on brainstem and thalamic mechanisms mediating the stimulus-induced cortical arousal.
The afferent humoral system exerts significant influences on brain activity. Central nervous actions of the adrenocorticotropic hormone (ACTH) are most likely to be mediated by information coded in a portion of this hormone structure corresponding to ACTH 4-10. Our previous research suggested an impairing effect of ACTH 4-10 on electrophysiological signs of selective attention in humans. The present experiments in 12 male subjects investigated the influences of ACTH 4-10 on different aspects of attention as indicated by auditory event-related potential (AERP) components. Furthermore, dose-response characteristics of these influences should be examined. Attention performance was tested in a dichotic listening paradigm, after 0, 0.1, 1.0, and 10 mg ACTH 4-10, administered intravenously 1 h prior to testing according to a double-blind latin-square design. Different aspects of attention were measured by brain electrical responses evoked either by frequent standard or rare target tone pips, which the subject had to attend to, or to ignore. The selective type of attention was reflected by the Nd determined as mean difference in amplitude between AERPs to tone pips when attended and when unattended, for a latency range between 0-460 ms post-stimulus. In addition, plasma cortisol, heart rate, blood pressure, and behavioral performance were measured. Results indicated a clear reduction of the Nd amplitude after all doses of ACTH 4-10. Other indicators of attention mechanisms such as mismatch processing were not affected by the peptide. The diminished Nd after ACTH 4-10 was due to an increased processing of unattended stimuli, but simultaneously attended tones were processed less intensively.(ABSTRACT TRUNCATED AT 250 WORDS)
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