Insulin receptor substrate-2 in the ventral tegmental area regulates behavioral responses to cocaine. |
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Authors: | I?iguez, Sergio D. Warren, Brandon L. Neve, Rachael L. Nestler, Eric J. Russo, Scott J. Bola?os-Guzmán, Carlos A. |
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Abstract: | Neurotrophic factor signaling modulates cellular and behavioral responses to drugs of abuse. Among other biochemical adaptations, chronic exposure to abused drugs decreases the expression of insulin receptor substrate-2 (IRS-2; a protein involved in neurotrophic signaling) in the ventral tegmental area (VTA), a neural substrate for many drugs of abuse. Using viral-mediated gene transfer to locally alter the activity of IRS-2, the authors show that overexpression of IRS-2 in the VTA results in an enhanced preference for environments previously paired with cocaine, as measured by the place conditioning paradigm, whereas blockade of IRS-2 activity results in avoidance of cocaine-paired compartments. In addition, IRS-2 overexpression leads to enhanced cocaine-induced locomotor activity, and blockade of IRS-2 expression significantly blunts behavioral responses to cocaine. These results demonstrate that levels of IRS-2 in the VTA regulate responsiveness to the behavioral effects of cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved) |
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Keywords: | growth factors neural plasticity viral-mediated gene transfer drug addiction behavioral sensitization behavioral responses cocaine rats |
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