Major Theme

            We currently use a rat model that has face, construct, and predictive validity with clinically depressed humans.  Individuals diagnosed with depression share many symptoms that are similar to rodents exposed to chronic stress, including anhedonia, altered body weight gain, and a dysregulated stress response.  In addition, both depressed patients and chronically stressed rodents express small hippocampal volumes and impaired hippocampal function, such as poor declarative and spatial memory.  Since depression and chronic stress and hippocampal dysfunction in common, then identifying the mechanisms that produce and prevent hippocampal damage after chronic stress in rodents may provide strategies for treating and preventing cognitive dysfunction in patients with depression.

Current Specific Research Areas

1. Investigation of mechanisms by which chronic stress leads to morphological changes in the hippocampus, a brain area involved in spatial memory.  We recently found that spatial memory deficits following chronic stress can be prevented by attenuating elevations of glucocorticoids (a stress steroid) on the day or memory assessment.  Future studies are planned to investigate this mechanism.  See Wright et al., (2006) Eur. J. Neurosci. 24: 595.

2. We are interested in determining what interventions may reduce or prevent the deleterious effects of chronic stress on the brain and behavior.  Our recent study presented at the 2006 Society for Neuroscience conference shows housing rats in an enriched environment prevents the cognitive deficits typically produced by chronic stress.  Future studies are aimed at identifying mechanisms that may permit environmental enrichment to benefit animals exposed to chronic stress.   See Wright and Conrad (2008) in Behav. Brain Res. 187: 41 and Coombs et al., (2008) presented at the Society for Neuroscience conference.

3. We are also interested in sex differences in the effects of chronic stress on the brain and behavior.  We have reported that females tend to perform better than males on tests of cognitive function following acute and chronic stress.  We are interested in determining mechanisms that may permit females to show intact or even facilitated spatial memory despite exposure to stress.  see Conrad et al., (2004) Pharmacol. Biochem. Behav. 78: 569, McLaughlin er al., (2005) Neuroscience, 135: 1045. and Baran et al., (2008) presented at the Society for Neuroscience conference.., 78, 569-579; McLaughlin et al., 2005, Neuroscience, 135, 1045-1054.)