Insulin receptor substrate-2 in the ventral tegmental area regulates behavioral responses to cocaine.

نویسندگان

  • Sergio D Iñiguez
  • Brandon L Warren
  • Rachael L Neve
  • Eric J Nestler
  • Scott J Russo
  • Carlos A Bolaños-Guzmán
چکیده

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.

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عنوان ژورنال:
  • Behavioral neuroscience

دوره 122 5  شماره 

صفحات  -

تاریخ انتشار 2008