Neuroplasticity, memory and drug-induced reinforcement in histamine H1-receptor- and histidine-decarboxylase knockout mice

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The role of neuronal histamine in learning and memory, neuroplasticity as well as drug-induced place preference will be studied using knockouts (KO) of the H1-receptor (H1-R) and the enzyme histidine-decarboxylase (HDC), which converts the precursor histidine to histamine. The HDC- and H1-R-KO mice will be evaluated in terms of delay-dependent object recognition, object-place memory, and temporal order memory. Histamine has been implicated in synaptic plasticity. Synaptic long-term potentiation- and depression will be measured in brain regions relevant to these different types of object memory (e.g., hippocampus, medial prefrontal -and perirhinal cortex). Since deficient episodic memory is the cardinal cognitive symptom in Alzheimer¿s disease, and since it¿s pathology also includes degeneration of histaminergic neurons, HDC- and H1-R-KO mice are to be tested in an episodic-like memory task. The brain s histamine system exerts inhibitory effects on the brain¿s reinforcement systems by an antagonistic action on the mesolimbic dopamine system. The H1-R- and HDC-KO mice will be examined for both morphine- and cocaine-induced place preference. By means of in-vivo microdialysis the effects of a behaviorally active dose of cocaine on extracellular dopamine levels in the neostriatum of freely moving HDC-C57BL/6-KO and wild type mice will be determined. HDC-KO mice will also be subjected to a morphometrical analysis of the mesolimbic dopamine system.