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Disrupting the melanin‐concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function
Author(s) -
Adamantidis Antoine,
Thomas Elizabeth,
Foidart Agnès,
Tyhon Amélie,
Coumans Bernard,
Minet Arlette,
Tirelli Ezio,
Seutin Vincent,
Grisar Thierry,
Lakaye Bernard
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04100.x
Subject(s) - nmda receptor , melanin concentrating hormone , hippocampal formation , neuroscience , receptor , knockout mouse , hippocampus , genetically modified mouse , inhibitory postsynaptic potential , endocrinology , chemistry , biology , medicine , transgene , biochemistry , gene , neuropeptide
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 in N ‐methyl d ‐aspartate (NMDA) responses in the hippocampus. Intracellular recordings of CA1 pyramidal neurons in hippocampal slices from the MCHR1 Neo/Neo mice revealed significantly decreased NMDA responses. Finally, using in situ hybridization 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.