deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors删除谷氨酸delta 1受体在小鼠会导致异常的情感和社会行为.pdfVIP

Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Aberrant Emotional and Social Behaviors 1 1 1 1 2 Roopali Yadav , Subhash C. Gupta , Brandon G. Hillman , Jay M. Bhatt , Dustin J. Stairs , Shashank M. Dravid1* 1 Department of Pharmacology, Creighton University, Omaha, Nebraska, United States of America, 2 Department of Psychology, Creighton University, Omaha, Nebraska, United States of America Abstract The delta family of ionotropic glutamate receptors consists of glutamate d1 (GluD1) and glutamate d2 (GluD2) receptors. While the role of GluD2 in the regulation of cerebellar physiology is well understood, the function of GluD1 in the central nervous system remains elusive. We demonstrate for the first time that deletion of GluD1 leads to abnormal emotional and social behaviors. We found that GluD1 knockout mice (GluD1 KO) were hyperactive, manifested lower anxiety-like behavior, depression-like behavior in a forced swim test and robust aggression in the resident-intruder test. Chronic lithium rescued the depression-like behavior in GluD1 KO. GluD1 KO mice also manifested deficits in social interaction. In the sociability test, GluD1 KO mice spent more time interacting with an inanimate object compared to a conspecific mouse. D-Cycloserine (DCS) administration was able to rescue social interaction deficits observed in GluD1 KO mice. At a molecular level synaptoneurosome preparations revealed lower GluA1 and GluA2 subunit expression in the prefrontal cortex and higher GluA1, GluK2 and PSD95 expression in the amygdala of GluD1 KO. Moreover, DCS normalized the lower GluA1 expression in prefrontal cortex of GluD1 KO. We propose that deletion of GluD1 leads to aberrant circuitr