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Modulation of Neuroendocrine Response and Non-Verbal Behavior during Psychosocial Stress in Healthy Volunteers by the Glutamate Release-Inhibiting Drug Lamotrigine

Makatsori A.a · Duncko R.a · Moncek F.a · Loder I.b · Katina S.c · Jezova D.a
aLaboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia; bInstitute of Adaptive and Spaceflight Physiology, Graz, Austria, and cDepartment of Probability and Mathematical Statistics, Faculty of Mathematics, Physics and CS, Comenius University, Bratislava, Slovakia Neuroendocrinology 2004;79:34–42 (DOI:10.1159/000076045)


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.


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