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Selective Antagonism of mGlu5 Alters Sleep‐wake and Spectral EEG and Ameliorates Behavioral Abnormalities in a Rodent Model of Traumatic Stress
Author(s) -
Nedelcovych Michael,
Gould Robert,
Gong Xuewen,
Felts Andrew,
Grannan Michael,
Thompson Analisa,
Ivarsson Magnus,
Emmitte Kyle,
Lindsley Craig,
Conn Jeffrey,
Jones Carrie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.615.8
Subject(s) - non rapid eye movement sleep , electroencephalography , psychology , neuroscience , sleep (system call) , computer science , operating system
Traumatic stress induces state‐dependent alterations in cortical network activity as measured by sleep‐wake and quantitative electroencephalography (qEEG) that may predict the onset or severity of chronic post‐traumatic stress disorder (PTSD) symptoms. Activation of metabotropic glutamate receptor 5 (mGlu5) promotes fear memory consolidation, and may contribute to sleep disturbances after trauma. The single prolonged stress (SPS) rodent model of traumatic stress recapitulates many physiological and behavioral correlates of the human disorder, but its effect on sleep‐wake and qEEG spectral power has not been examined. Male Sprague‐Dawley rats were implanted with telemetric EEG electrodes continuously recording cortical activity before and after SPS. VU0409106, a selective mGlu5 negative allosteric modulator (NAM) was administered after SPS to assess blockade or reversal of SPS‐induced sleep‐wake and qEEG disturbances. SPS caused persistent PTSD‐like alterations in rapid eye movement (REM) sleep and non‐REM (NREM) sleep as well as changes in state‐dependent spectral power, such as an increase in waking beta (18‐30Hz) power, and a decrease in NREM delta (0.5‐4Hz) power indicative of hyperarousal and poor sleep quality. VU0409106 modulated SPS‐induced sleep‐wake architecture changes and qEEG spectral power alterations and ameliorated accompanying anxiety‐like behaviors.