Vol 6 n° 2 - Neuroplasticity
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eural plasticity is a fundamental process that allows the brain to receive information and form appro- priate adaptive responses to the same or similar stimuli. The molecular and cellular adaptations underlying learn- ing and memory are the best-characterized and most- studied examples of neural plasticity. However, many different stimuli can activate neural plasticity processes in different brain structures, including environmental, social, behavioral, and pharmacological stimuli. In fact, it could be argued that neural plasticity is one of the most essential and important processes that the brain performs as it relates to many types of central nervous system functions. Thus, disrupted or abnormal plasticity could lead to mal- adaptive neuronal responses and abnormal behavior. This could occur in response to genetic abnormalities of the cellular machinery required for plasticity, and abnor- mal or inappropriate stimuli. For example, exposure to inappropriate or prolonged stress has been reported to alter molecular and cellular markers of neural plasticity, and could contribute to stress-related mood disorders. This review will discuss the literature demonstrating altered neural plasticity in response to stress, and clini- cal evidence indicating that altered plasticity occurs in depressed patients. The second part of the review will present evidence that antidepressant treatment blocks the effects of stress or produces plasticity-like responses. General mechanisms of neural plasticity Neural plasticity encompasses many different types of molecular and cellular responses that occur when cells in the brain are induced to respond to inputs from other 1 5 7 P h a r m a c o l o g i c a l   a s p e c t s N Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Neural plasticity: consequences of stress and actions of antidepressant treatment Ronald S. Duman, PhD Neural plasticity is emerging as a fundamental and crit- ical mechanism of neuronal function, which allows the brain to receive information and make the appropriate adaptive  responses  to  subsequent  related  stimuli. Elucidation of the molecular and cellular mechanisms underlying neural plasticity is a major goal of neuro- science research, and significant advances have been made in recent years. These mechanisms include regula- tion of signal transduction and gene expression, and also structural alterations of neuronal spines and processes, and even the birth of new neurons in the adult brain. Altered plasticity could thereby contribute to psychiatric and neurological disorders. This article reviews the liter- ature demonstrating altered plasticity in response to stress, and evidence that chronic antidepressant treat- ment can reverse or block the effects, and even induce neural plasticity-like responses. Continued elucidation of the mechanisms underlying neural plasticity will lead to novel drug targets that could prove to be effective and rapidly acting therapeutic interventions.   © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:157-169. Keywords: signal transduction; gene expression; neurotrophic factor; neurogenesis; neuronal atrophy Author   affiliations:   Division   of   Molecular   Psychiatry,   Departments   of Psychiatry  and  Pharmacology,  Yale  University  School  of  Medicine,  New Haven, CT, USA Address for correspondence: Ronald S. Duman, PhD, 34 Park Street, New Haven, CT 06508, USA (e-mail: ronald.duman@yale.edu)