K. H. Voigt

Vasopressin and electrophysiological signs of attention in man

Seventeen pairs of monozygotic twins, females and males, were tested in a dichotic listening task, containing several types of pips: standard and deviating target pips, which the subject either attended to, or not. Averaged auditory evoked potentials (AEPs) to the pips provided measures of different attentional processes. Furthermore, EEG power spectra, heart rate and blood pressure and behavioral performance were measured. Subjects received treatments (20 I.U. lysine-vasopressin vs. placebo) intranasally 48, 24, and 1 hour prior to the experimental sessions according to a co-twin control design. Whereas measures of voluntary selective attention remained unchanged by lysine-vasopressin (LVP) the peptide primarily affected an attentional mechanism responding in an automatic fashion to stimulus deviance. This effect was indicated by a substantial negative shift of the AEP amplitudes following deviating stimuli within the latency range of the N2/P2 components (about 200 msec post-stimulus). The effect seemed to be unrelated to modulations of cortical arousal after LVP.

Paradoxical ACTH Response to Glucocorticoids in Cushing's Disease

To define further the defect in the steroid feedback mechanism in Cushings disease, we studied the acute effects of intravenous administration of glucorticoids on plasma ACTH levels in seven patients with this disease after total adrenalectomy. In seven other patients with hypoadrenocorticism ACTH was readily suppressed; a significant decrease (72.5+/-5 per cent, mean +/- S.E.M., P less than 0.002) occurred within 15 minutes of the start of an infusion of 50 mg per hour of cortisol. In contrast, in the seven adrenalectomized patients with Cushings disease, cortisol induced a transient paradoxical rise in ACTH levels, with a maximum at 15 minutes (347+/-99 per cent,, P less than 0.05). A similar ACTH response was observed with dexamethasone. Cushings disease is characterized by a paradoxical transient rise in ACTH after glucocorticoid administration. This effect was more pronounced in adrenalectomized than in nonadrenalectomized patients.

Effect of an ACTH 4–9 analog on human cortical evoked potentials in a constant foreperiod reaction time paradigm

Abstract Thirty male volunteers, receiving either 40 mg ACTH 4–9 analog (Org 2766) or 40 mg placebo in a double-blind setting, participated in an experiment which investigated cortical evoked potentials, slow cortical potentials, EEG power spectrum, heart rate and response speed within a constant foreperiod reaction time paradigm. EEG was recorded frontally, precentrally and parietally. Subjects receiving Org 2766 responded significantly faster than placebo controls. Larger or advanced evoked potential components, a smaller late slow wave component, a tendency for more activity in lower alpha range and more pronounced decrease in mean heart rate across trials were found in peptide subjects as compared to placebo controls. These results suggest an effect of Org 2766 on cortical processes associated with early stimulus selection and processing.

Dishabituating effects of an ACTH 4–9 analog in a vigilance task

Ten male adults were tested in a vigilance task after oral administration of either 40 mg ACTH 4-9 analog, ORG 2766, or placebo in a single three hour session. EEG spectra, averaged auditory evoked responses, heart rate and blood pressure, and behavioral performance were measured during a vigilance task. ACTH 4-9 analog treatment led to a decreased inhibition of the central nervous system across the experiment: to less mean power density and faster center frequencies within the alpha band, and to less attenuated amplitudes of the components of the auditory vertex potential (P50, N100, P200). Treatment effects increased towards the end of the session and might indicate a dishabituating effect, probably due to suppression of inhibitory influences of limbic structures on mesencephalic reticular activity.

Hypothalamo-posterior pituitary system in Brattleboro rats: Immunoreactive levels of leucine-enkephalin, dynorphin (1–17), dynorphin (1–8) and α-neo-endorphin

The levels of immunoreactive leucine-enkephalin, alpha-neo-endorphin, dynorphin (1-17) and dynorphin (1-8) have been determined in the hypothalamus and posterior pituitary from male and female Brattleboro rats homozygous (unable to produce vasopressin) and heterozygous (producing vasopressin) for diabetes insipidus, and from male and female Long Evans rats. In the hypothalamus we found no significant differences in the levels of these peptides while there were great differences in extracts from the posterior pituitary: female homozygous animals have greatly reduced levels in all four peptides compared to the heterozygous controls. In male homozygous animals the differences in the dynorphin (1-17) and leucine-enkephalin levels were small whereas the concentrations of alpha-neo-endorphin and dynorphin (1-8) showed a significant decrease compared to the male heterozygous controls. The results indicate a reduction in opioid peptides linked to the vasopressin deficiency in a partially sex dependent manner.

Influences of ACTH 4-10 on event-related potentials reflecting attention in man.

The present paper is concerned with effects of the 4-10 sequence of the endogenous ACTH on electrophysiological measures of attention in humans. It was attempted to replicate previous findings of an impaired selective attention following administration of an analog of ACTH 4-9. The effect of this analog had been found to dominate in the beginning of the blocks of an attention task, but to fade away with time on task. In the present study, fourteen male students were tested in a dichotic listening paradigm, 40 min after intranasal application of either 0.4 mg ACTH 4-10, or placebo. Averaged auditory evoked potentials (AEPs) to attended and inattended tone pips, EEG power spectra, heart rate and blood pressure, and behavioral performance were measured during task performance. ACTH 4-10 appeared to slightly impair selective attention as indicated by AEP responses. In particular, the positive shift of the AEP waveforms to inattended stimuli was reduced at the beginning of each block of tone pips under ACTH 4-10. The pattern of actions resembled the effects observed after administration of the more potent synthetic analog of ACTH 4-9 in the previous experiment. Effects of ACTH 4-10 on the AEPs to inattended stimuli, however, differed from influences of the synthetic analog in that they did not affect a rather wide latency range but concentrated on the latency range of the P200 component.

Effects of an ACTH 4-9 analog on auditory evoked brainstem responses and middle latency responses.

Early and middle latency auditory evoked potentials (EAEPs and MAEPs) were recorded from thirteen male volunteers after oral administration of either 40 mg of an ACTH 4-9 analog (ORG 2766) or placebo. Main results indicate slightly longer latencies of the later components of the EAEPs after ACTH 4-9 analog. Effects of differences in treatment were clearest with very high stimulus rates. Therefore, these effects do not lend themselves for the explanation of ACTH 4-9 analog-induced changes in long latency auditory evoked potentials of cortical origin obtained with comparatively slow stimulus rates in earlier studies. In addition, the ACTH 4-9 analog inhibited a decrease in amplitudes of the Na component of the MAEP across the session. This latter result may be in line with dishabituating actions of the peptide.

ACTH and Cortisol Secretion in Cushing’s Disease and in Endogenous Depression: Indication of a Common Pathway?

An impaired regulation of Cortisol secretion can be observed in patients suffering from one of two otherwise unrelated diseases: The hypothalamo-pituitary- dependent Cushing’s Syndrome and a subpopulation of major depressive illness. Among a number of different other disturbances of neuroendocrine regulations (Table 1) the cortisol-hypersecretion is the most important and the typical diagnostic sign for Cushing’s disease, and on the other hand, the most consistently observed hormonal dysregulation in endogenously depressed patients.