Scott J. Russo

Research

Overview
The lab uses a wide variety of experimental approaches to understand how the brain adapts to stress and drugs leading to altered synaptic connectivity and behavioral changes relevant to depression and addiction.  We do this by integrating well-established behavioral models, with molecular and biochemical techniques and traditional neuroanatomy.

Neurobiological mechanisms of stress
Aberrant growth or retraction of dendritic spines and neurite processes have been implicated in a multitude of psychiatric and neurological diseases, including drug addiction, stress disorders, X-linked mental retardation and schizophrenia. Features of these diseases often include one or more of the following: reward dysfunction and memory deficits, anxiety and depressed mood, hyperarousal and exaggerated startle responses. Many of these symptoms are core features of anxiety and mood disorders in humans and can be modeled to some extent, using chronic stress models in mice. The field currently uses a range of mild to severe stressors to study the behavioral symptoms of anxiety and depression and it is well established that stress can strongly influences neuronal morphology in key brain reward regions. We are currently uncovering fundamental biochemical pathways regulated by stress to alter cellular connectivity in brain reward regions to define more selective drug targets that reduce side effects and more effectively treating the core behavioral symptoms of depression and anxiety.   

Gender and depression
The effects of chronic stress on neural and behavioral plasticity are far less characterized in female rodents compared with male rodents, despite the predominance of the human syndrome in women.  In my lab we study biological determinants of sex differences in stress-induced depressive behavior.  Although the biological mechanisms are not fully understood, it's likely that a female's increased sensitivity to stress-induced depressive-like behaviors is related to the presence of fluctuating ovarian hormones.  In a recent study we showed that surgical ovariectomy blunted stress-induced gene expression in nucleus accumbens and decreased their sensitivity to stress induced depressive behavior. The goal of these studies are to uncover gender specific molecular targets for drug development to improve treatment outcomes for woman suffering from depression.

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