Effects of L‐histidine depletion and L‐tyrosine/L‐phenylalanine depletion on sensory and motor processes in healthy volunteers

Abstract

Background and purpose:Animal studies show that histamine plays a role in cognitive functioning and that histamine H3-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 H1-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 H1-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.

Dietary Tyrosine/Phenylalanine Depletion Effects on Behavioral and Brain Signatures of Human Motivational Processing

“…His competes with other LNAAs for transit into the brain, where it is transformed into histamine, such that His restriction holds the potential for an antihistaminelike sedative effect. In a degraded-stimulus signal-detection task, however, His depletion only mildly affected some taskelicited EEG signatures, but did not significantly affect RTs or accuracy of signal detection (van Ruitenbeek et al, 2009). Similarly, RTs in this experiment were substantially similar to those of controls in the previous study with this MID variant (Bjork et al, 2008) that featured no pharmacological manipulation.…”

How Human Electrophysiology Informs Psychopharmacology: from Bottom-up Driven Processing to Top-Down Control

“…Van Ruitenbeek et al (2009a) investigated the effect of L-histidine depletion (assumed to reduce central histamine availability). Stimulus degradation and response complexity slowed down RT additively, but these effects did not interact with those of treatment, nor was their any main effect of treatment (this also held for accuracy).…”

Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

“…In a human study, a histidine-deficient amino acid mixture lowered plasma histidine and changed responses in some laboratory measures of behaviour. 79 Therefore, a tryptophanand histidine-deficient amino acid mixture might influence the function of both serotonin and histamine. The absence of histidine from the control mixture would mean that histamine might be low in both control participants and in those receiving the deficient mixture.…”