Stress-induced deficits in cognition and emotionality: a role of glutamate.

Abstract

Stress is associated with a number of neuropsychiatric disorders, many of which are characterized by altered cognition and emotionality. Rodent models of stress have shown parallel behavioral changes such as impaired working memory, cognitive flexibility and fear extinction. This coincides with morphological changes to pyramidal neurons in the prefrontal cortex, hippocampus and amygdala, key cortical regions mediating these behaviors. Increasing evidence suggests that alteration in the function of the glutamatergic system may contribute to the pathology seen in neuropsychiatric disorders. Stress can alter glutamate transmission in the prefrontal cortex, hippocampus and amygdala and altered glutamate transmission has been linked to neuronal morphological changes. More recently, genetic manipulations in rodent models have allowed for subunit-specific analysis of the role of AMPA and NMDA receptors as well as glutamate transporters in behaviors shown to be altered by stress. Together these data point to a role for glutamate in mediating the cognitive and emotional changes observed in neuropsychiatric disorders. Furthering our understanding of how stress affects glutamate receptors and related signaling pathways will ultimately contribute to the development of improved therapeutics for individuals suffering from neuropsychiatric disorders.