[en] 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Adamantidis, Antoine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Thomas, Elizabeth
Foidart, Agnès ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Service administratif de la Faculté (Médecine)
Tyhon, Amélie ; Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.
Coumans, Bernard ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Minet, Arlette ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Tirelli, Ezio ; Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.
Seutin, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Grisar, Thierry ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Lakaye, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Language :
English
Title :
Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function.
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