Author:
Dere Ekrem,De Souza-Silva Maria A.,Topic Bianca,Spieler Richard E.,Haas Helmut L.,Huston Joseph P.
Abstract
The brain's histaminergic system has been implicated in hippocampal
synaptic plasticity, learning, and memory, as well as brain reward and
reinforcement. Our past pharmacological and lesion studies indicated that the
brain's histamine system exerts inhibitory effects on the brain's
reinforcement respective reward system reciprocal to mesolimbic dopamine
systems, thereby modulating learning and memory performance. Given the close
functional relationship between brain reinforcement and memory processes, the
total disruption of brain histamine synthesis via genetic disruption of its
synthesizing enzyme, histidine decarboxylase (HDC), in the mouse might have
differential effects on learning dependent on the task-inherent reinforcement
contingencies. Here, we investigated the effects of an HDC gene disruption in
the mouse in a nonreinforced object exploration task and a negatively
reinforced water-maze task as well as on neo- and ventro-striatal dopamine
systems known to be involved in brain reward and reinforcement. Histidine
decarboxylase knockout (HDC-KO) mice had higher dihydrophenylacetic acid
concentrations and a higher dihydrophenylacetic acid/dopamine ratio in the
neostriatum. In the ventral striatum, dihydrophenylacetic acid/dopamine and
3-methoxytyramine/dopamine ratios were higher in HDC-KO mice. Furthermore, the
HDC-KO mice showed improved water-maze performance during both hidden and cued
platform tasks, but deficient object discrimination based on temporal
relationships. Our data imply that disruption of brain histamine synthesis can
have both memory promoting and suppressive effects via distinct and
independent mechanisms and further indicate that these opposed effects are
related to the task-inherent reinforcement contingencies.
Publisher
Cold Spring Harbor Laboratory
Subject
Cellular and Molecular Neuroscience,Cognitive Neuroscience,Neuropsychology and Physiological Psychology
Cited by
85 articles.
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