Neuronal histamine and the interplay of memory, reinforcement and emotions

Neuronal histamine and cognitive symptoms in Alzheimer's disease

“…In conclusion, the cognitive phenotyping of HDC deficient mice has yielded a mixture of task-dependent learning and memory impairments, unaffected performance, but also improvements in learning and memory (Dere et al, 2004(Dere et al, , 2003 [which might be due to motivational/emotional changes (Dere et al, 2004)]. This variability in mnemonic functions in HDC deficient mice might be related to an increased or decreased motivation to learn in dependence of the reinforcement contingencies of the specific learning task used (Dere et al, 2003(Dere et al, , 2010. Additionally, it should be considered that the HDC deficient and control mice had a pure 129/Sv genetic background and that this substrain is known to exhibit a number of behavioral peculiarities in contrast to the C57BL/6 strain which is the most commonly used genetic background strain in the field of mouse behavioral genetics.…”

“…However, it is now increasingly recognized that other pathologies, for example alterations in the neuronal histaminergic system, also contribute to the cognitive impairments displayed by these patients (Blandina et al, 2004;Dere et al, 2010;Mazurkiewicz-Kwilecki et al, 1989;Passani et al, 2011). Alzheimer's disease patients show alterations of histamine concentrations in the brain (Airaksinen et al, 1991a(Airaksinen et al, , 1991bPanula et al, 1989), reduced histamine releasing factor levels, decreased quantities of H1R in the frontal cortex and temporal cortex as well as degeneration of histamine neurons in the tuberomamillary nucleus (Airaksinen et al, 1991a(Airaksinen et al, , 1991bSaper et al, 1987).…”

“…There is evidence for a promnestic effect of histamine and histamine receptor stimulation in aged rodents (Dere et al, 2010). Procognitive effects of histamine receptor stimulation have been observed in cholinergic deficit animal models of Alzheimer's disease, where a memory impairment is induced by cholinergic lesions of the basal forebrain (Chen and Shen, 2002) or by the preadministration of amnestic drugs such as scopolamine (Yamamoto et al, 2007) or MK-801 (Xu et al, 2005).…”

“…The behavioral effects of histamine-related mouse mutants including HDC, H1, H2, and H3 knockout mice have been extensively reviewed in by Schneider et al (2014aSchneider et al ( , 2014b and Dere et al (2010). In the following we will concentrate on the behavioral and neurochemical phenotypes of HDC and H1R knockout mice.…”

“…Regarding the potential use of H1R antagonists in Alzheimer's disease, one has to consider that the effect of H1R antagonists on cognitive performance of rats and mice is quite complex. Both improvements and impairments in cognitive behavior have been reported after H1R antagonism depending on the reinforcement contingencies of the behavioral paradigm, motivational status and the stress-level experienced by the animal (for review see (Dere et al, 2010). Given that H1R antagonism can impair cognitive performance and given that H1R knockout mice show a dementia-like phenotype together with impaired neurogenesis (Ambree et al, 2014;Dere et al, 2008;Zlomuzica et al, 2013Zlomuzica et al, , 2009Zlomuzica et al, , 2008, it remains to be determined whether the possible beneficial effects of H1R antagonists on neuroinflammation would justify the concomitant adverse effects on cognition and adult neurogenesis in patients with Alzheimer's disease.…”