Deficits in cognitive flexibility induced by chronic unpredictable stress are associated with impaired glutamate neurotransmission in the rat medial prefrontal cortex

• Published in: Neuroscience 2017-03, Vol.346, p.284-297
• Main Authors: Jett, Julianne D, Bulin, Sarah E, Hatherall, Lauren C, McCartney, Carlie M, Morilak, David A
• Format: Article
• Language: English
• Subjects: Animals; Attention - drug effects; Attention - physiology; attentional set-shifting; chronic unpredictable stress; Cognition - drug effects; Cognition - physiology; cognitive flexibility; Cytoskeletal Proteins - metabolism; glutamate; Glutamic Acid - metabolism; Glutamic Acid - physiology; Hippocampus - physiopathology; Male; medial prefrontal cortex; Mediodorsal Thalamic Nucleus - drug effects; Mediodorsal Thalamic Nucleus - physiology; mediodorsal thalamus; Nerve Tissue Proteins - metabolism; Neurology; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Proto-Oncogene Proteins c-jun - metabolism; Rats; Rats, Sprague-Dawley; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - physiology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Synaptic Transmission
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2017.01.017

Highlights • Depression is associated with cognitive flexibility deficits and mPFC hypoactivity. • Chronic unpredictable stress (CUS) induces cognitive flexibilty deficits. • CUS attenuated mPFC response to afferent activation and acute increases in glutamate. • NMDA or AMPA, but not mGlur5, antagonists in mPFC compromised set-shifting. • Thus glutamate dysregulation in mPFC could underly cognitive deficits after CUS. • Glutamate signaling is a viable therapeutic target for cognitive deficits in depression.