Potential enhancing effects of histamine H-1 agonism/H-3 antagonism on working memory assessed by performance and bold response in healthy volunteers

TY - JOUR

T1 - Potential enhancing effects of histamine H-1 agonism/H-3 antagonism on working memory assessed by performance and bold response in healthy volunteers

AU - van Ruitenbeek, P.

AU - Mehta, M. A.

PY - 2013/9

Y1 - 2013/9

N2 - Background and Purpose  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 H-3 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 (H-3 antagonist/H-1 agonist) on learning and memory, and associated brain activity were assessed. Experimental Approach  Sixteen healthy volunteers (eight female) aged between 18 and 50 years received two p.o. doses of betahistine (48mg) or placebo separated by 30min, 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. Key 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 and Implications  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.

AB - Background and Purpose  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 H-3 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 (H-3 antagonist/H-1 agonist) on learning and memory, and associated brain activity were assessed. Experimental Approach  Sixteen healthy volunteers (eight female) aged between 18 and 50 years received two p.o. doses of betahistine (48mg) or placebo separated by 30min, 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. Key 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 and Implications  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.

KW - H-3 antagonist

KW - H-1 agonist

KW - betahistine

KW - learning

KW - memory

KW - histamine

KW - human cognition

KW - imaging

KW - MRI

U2 - 10.1111/bph.12184

DO - 10.1111/bph.12184

M3 - Article

SN - 0007-1188

VL - 170

SP - 144

EP - 155

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

IS - 1

M1 - N/A

ER -