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

Sergio D Iñiguez1, Brandon L Warren, Rachael L Neve

  • 1Department of Psychology, Florida State Universit, FL, USA.

Behavioral Neuroscience
|October 1, 2008
PubMed

Insights

Insulin receptor substrate-2 (IRS-2) levels in the ventral tegmental area (VTA) regulate responses to cocaine. Lower IRS-2 reduces cocaine

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Addiction Research

Background:

  • Neurotrophic factor signaling influences responses to drugs of abuse.
  • Chronic drug exposure reduces insulin receptor substrate-2 (IRS-2) expression in the ventral tegmental area (VTA).

Purpose of the Study:

  • To investigate the role of IRS-2 in the VTA in mediating behavioral responses to cocaine.

Main Methods:

  • Utilized viral-mediated gene transfer to manipulate IRS-2 expression in the VTA.
  • Assessed cocaine-induced place preference and locomotor activity using the place conditioning paradigm.

Main Results:

  • Overexpression of IRS-2 in the VTA enhanced cocaine-associated place preference.
  • Blockade of IRS-2 activity in the VTA led to avoidance of cocaine-paired environments.
  • IRS-2 overexpression potentiated cocaine-induced locomotor activity, while blockade blunted these effects.

Conclusions:

  • VTA IRS-2 levels are critical regulators of behavioral plasticity induced by cocaine.
  • IRS-2 signaling in the VTA modulates an individual's responsiveness to the rewarding and motor effects of cocaine.

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