title: Potential enhancing effects of histamine H₁ agonism/H₃ antagonism on working memory assessed by performance and bold response in healthy volunteers.
abstract: OBJECTIVE
  Schizophrenia is a highly debilitating disorder characterized by hallucinations and delusions, but also impaired cognition such as memory. While hallucinations and delusions are the main target for pharmacological treatment, cognitive impairments are rarely treated. Evidence exists that histamine has a role in the cognitive deficits in schizophrenia, which could be the basis of the development of a histamine-type treatment. Histamine H₃ antagonists have been shown to improve memory performance in experimental animals, but these effects have been little investigated in humans within the context of impaired cognition in schizophrenia and using sensitive measures of brain activity. In the present study, the effects of betahistine (H₃ antagonist/H₁ agonist) on learning and memory, and associated brain activity were assessed.
  
  
  METHODS
  Sixteen healthy volunteers (eight female) aged between 18 and 50 years received two p.o. doses of betahistine (48 mg) or placebo separated by 30 min, on separate days according to a two-way, double-blind, crossover design. Volunteers performed an N-back working memory task and a spatial paired associates learning task while being scanned using a MRI scanner.
  
  
  RESULTS
  Task-related activity changes in well-defined networks and performance were observed. No betahistine-induced changes in brain activity were found in these networks. Alternatively, liberal whole-brain analyses showed activity changes in areas outside task networks, like the lateral geniculate nucleus.
  
  
  CONCLUSIONS
  Clear effects of betahistine on working memory could not be established. Future studies should use higher doses and explore the role of histamine in visual information processing.
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, UK. peter.vanruitenbeek@faber.kuleuven.be
authors.forename: P
authors.initials: P
authors.lastname: van Ruitenbeek
authors.forename: M A
authors.initials: MA
authors.lastname: Mehta
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001621:Betahistine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D017442:Histamine Agonists / Q000494:pharmacology*; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D006801:Humans; D007858:Learning / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D001621:Betahistine
keywords: H1 agonist; H3 antagonist; MRI; betahistine; histamine; human cognition; imaging; learning; memory