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Histamine H 1 receptor knockout mice exhibit impaired spatial memory in the eight‐arm radial maze
Author(s) -
Zlomuzica A,
Ruocco LA,
Sadile AG,
Huston JP,
Dere E
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.1476-5381.2009.00225.x
Subject(s) - histaminergic , neuroscience , autoreceptor , hippocampus , histamine receptor , morris water navigation task , working memory , endocrinology , receptor , barnes maze , knockout mouse , psychology , water maze , medicine , cholinergic , agonist , biology , antagonist , spatial learning , cognition
Background and purpose: In the mammalian brain, histaminergic neurotransmission is mediated by the postsynaptic histamine H 1 and H 2 receptors and the presynaptic H 3 autoreceptor, which also acts as a heteroreceptor. The H 1 receptor has been implicated in spatial learning and memory formation. However, pharmacological and lesion studies have revealed conflicting results. To examine the involvement of histamine H 1 receptor in spatial reference and working memory formation, H 1 receptor knockout mice (KO) were tested in the eight‐arm radial maze. Previously, we found that the H 1 receptor‐KO mice showed reduced emotionality when confronted with spatial novelty. As it is known that emotions can have an impact on spatial learning and memory performance, we also evaluated H 1 receptor‐KO mice in terms of emotional behaviour in the light–dark box. Experimental approach: Mice lacking the H 1 receptor and wild‐type mice (WT) were tested for spatial reference and working memory in an eight‐arm radial maze with three arms baited and one trial per day. Emotional behaviour was measured using the light–dark test. Key results: The H 1 receptor‐KO mice showed impaired spatial reference and working memory in the radial maze task. No significant differences between H 1 receptor‐KO and WT mice were observed in the light–dark test. Conclusions and implications: The spatial memory deficits of the H 1 receptor‐KO mice might be due to the reported changes in cholinergic neurochemical parameters in the frontal cortex and the CA1 subregion of the hippocampus, to impaired synaptic plasticity in the hippocampus, and/or to a dysfunctional brain reward/reinforcement system.