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Effects of L‐histidine depletion and L‐tyrosine/L‐phenylalanine depletion on sensory and motor processes in healthy volunteers
Author(s) -
Van Ruitenbeek P,
Sambeth A,
Vermeeren A,
Young SN,
Riedel WJ
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00203.x
Subject(s) - histaminergic , histamine , neuroscience , stimulus (psychology) , psychology , cognition , histidine decarboxylase , histamine h3 receptor , pharmacology , histidine , receptor , medicine , chemistry , antagonist , cognitive psychology , biochemistry , amino acid
Background and purpose: Animal studies show that histamine plays a role in cognitive functioning and that histamine H 3 ‐receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H 1 ‐receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L‐histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event‐related‐potentials) effects. Experimental approach: Seventeen healthy volunteers completed a three‐way, double‐blind, crossover study with L‐histidine depletion, L‐tyrosine/L‐phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed. Key results: Measures of sedation and critical tracking task performance were not affected by treatment. L‐histidine depletion was effective and enlarged the effect of response complexity as measured with the response‐locked lateralized readiness potential onset latency. Conclusions and implications: L‐histidine depletion affected response‐ but not stimulus‐related processes, in contrast to the effects of H 1 ‐receptor antagonists which were previously found to affect primarily stimulus‐related processes. L‐histidine depletion is promising as a model for histamine‐based cognitive impairment. However, these effects need to be confirmed by further studies.