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

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.

published proceedings

  • Behav Neurosci

altmetric score

  • 1

author list (cited authors)

  • Iiguez, S. D., Warren, B. L., Neve, R. L., Nestler, E. J., Russo, S. J., & Bolaos-Guzmn, C. A.

citation count

  • 23

complete list of authors

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

publication date

  • January 2008