학술논문
Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function.
Document Type
Article
Author
Source
Subject
*HORMONE receptors
*MELANINS
*COGNITION disorders
*MEMORY disorders
*METHYL aspartate
*IN situ hybridization
*LABORATORY mice
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Language
ISSN
0953-816X
Abstract
In order to investigate the physiological properties of the melanin-concentrating hormone (MCH) we have generated and used mice from which the MCH receptor 1 gene was deleted (MCHR1 Neo/Neo mice). Complementary experimental approaches were used to investigate alterations in the learning and memory processes of our transgenic model. The ability of the knockout strain to carry out the inhibitory passive avoidance test was found to be considerably impaired although no significant differences were observed in anxiety levels. This impaired cognitive property prompted us to explore modifications inN-methyld-aspartate (NMDA) responses in the hippocampus. Intracellular recordings of CA1 pyramidal neurons in hippocampal slices from theMCHR1 Neo/Neo mice revealed significantly decreased NMDA responses. Finally, usingin situhybridization we found a 15% reduction in NMDAR1 subunit in the CA1 region. These results show for the first time a possible role for MCH in the control of the function of the NMDA receptor. [ABSTRACT FROM AUTHOR]