The present work was aimed at verifying the following hypotheses: (a) lamotrigine, a drug used to treat mood disorders, affects regulation of stress hormone release in humans, and (b) non-verbal behavior during mental stress situations (public speech) is related to hormonal responses. To achieve these aims, we performed a controlled, double-blind study investigating hormonal responses and non-verbal behavior during public speech in healthy subjects with placebo or lamotrigine (300 mg per os) pretreatment. The stress procedure was performed in 19 young healthy males 5 h following drug or placebo administration. Data were obtained from cardiovascular monitoring, blood and saliva samples, as well as the video-recorded speech. Pre-stress hormone levels were not affected by lamotrigine treatment. Lamotrigine significantly inhibited diastolic blood pressure, growth hormone and cortisol increases during psychosocial stress. In contrast, it potentiated plasma renin activity and aldosterone responses. Non-verbal behavior analysis revealed a correlation between catecholamines and submissive or flight behavior in controls, while between catecholamines and displacement behavior following lamotrigine administration. In conclusion, effects of lamotrigine on hormone release might be of value for its mood-stabilizing action used in the treatment of bipolar disorder. The data are in support of a stimulatory role of glutamate in the control of cortisol and growth hormone release during psychosocial stress in humans; however, further studies using more selective drugs are needed to prove this suggestion. The effects on plasma renin activity and aldosterone release observed seem to be related to other actions of lamotrigine.
The relationship between anxiety and the neuroendocrine response to stress stimuli is still not fully understood. The aim of this study was to evaluate the contribution of an acute increase in state anxiety to neuroendocrine activation under stress conditions. To do so, it was necessary to find a stress condition of the same character and intensity with and without a rise in state anxiety. We decided to examine the effects of listening to music on anxiety and to apply a new methodological approach. A group of 14 healthy volunteers participated in a counterbalanced crossover design study. The stress procedure consisted of mental (Stroop test, mental arithmetic) and physical (handgrip exercise) tasks combined with listening to music played forward (pleasant) or backwards (unpleasant). The results confirmed our hypothesis, namely the condition with listening to unpleasant music was anxiogenic, while the other was not. In case of increased state anxiety, the rise in ACTH concentrations in response to mental challenge and the increase in systolic blood pressure induced by handgrip exercise was reduced compared to the situation with unchanged anxiety. Concentrations of testosterone, oxytocin, vasopressin and aldosterone were slightly increased in response to the stress paradigm accompanied with increased anxiety. In conclusion, the present data demonstrate that an acute increase in state anxiety contributes to neuroendocrine activation under stress conditions. Moreover, the results show that listening to music may both positively and negatively influence the perception of stress and the level of anxiety, which might have functional consequences.
Four men established a new score (Guinness Book of Records) by staying submersed in thermoneutral water (average diving depth 2.5 m) for 41 h without sleeping. The aim of this study is to measure circulating hormones together with plasma mass density and total protein concentration as indices of plasma volume change to test the hypotheses that (1) blood volume and related hormones are influenced by prolonged water submersion the same way as observed after short-term water immersion, and (2) plasma adrenomedullin levels change in an opposite fashion as with orthostatic stimulation. We also studied effects on cortisol and testosterone levels. Water submersion led to a 19% increase in plasma protein concentration and a 2.5 g/l rise in plasma mass density, corresponding to a 15.6+/-1.1% plasma volume decrease (P=0.00). We therefore individually corrected (c) the observed post-submersion hormone values for plasma volume contraction. Based on this correction, we found a rise of plasma adrenomedullin from 7.9+/-0.9 to 12.5(c)+/-2.3 pg/ml. Aldosterone rose from 123+/-14 to 186(c)+/-24 ng/ml (P=0.029); plasma renin activity increased in all four persons but the type I error was >0.05. Plasma testosterone decreased from 3.5+/-0.4 to 2.2(c)+/-0.6 ng/ml (P=0.009) while plasma cortisol stayed unchanged. The daily salivary cortisol rhythm was preserved. We conclude that long-term water submersion has endocrine as well as plasma volume effects that are opposite to those seen after short-term immersion, and which increases plasma adrenomedullin. Circadian cortisol rhythm seems to be conserved even under extreme circumstances as those of this study.
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