Molecular and Cellular Determinants of Stress and Antidepressant Treatment

Abstract

Studies to characterize the complex actions of stress and antidepressant treatment on brain function have made significant progress over the past 20 yr. This work demonstrates that in addition to regulation of neurotransmitter and neuroendocrine pathways, stress and antidepressant treatment also exert potent effects on neuronal morphology, cytoarchitecture, and intracellular signal transduction pathways. Moreover, progress is being made in understanding the molecular and cellular actions of stress in the context of the cellular and molecular systems that are thought to be involved in depression. The major first messengers involved in the action of stress and antidepressant treatment are the adrenal-glucocorticoids and monoamines. In addition, a role for excitatory amino acids and neurotrophic factors has been demonstrated. This chapter will briefly review the intracellular signaling pathways for each of these first messengers and then provide a more detailed analysis of these intracellular pathways in the context of stress and antidepressant treatment. Although a great deal of work still remains, this work has already begun to elucidate how alterations of these pathways may contribute to the pathophysiology and treatment of depression.