Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression

Behav Brain Res. 2011 Jan 1;216(1):463-5. doi: 10.1016/j.bbr.2010.07.034. Epub 2010 Aug 3.


Identifying new treatment approaches for treatment resistant depression (TRD) is an important topic for translational psychiatry. Functional inhibition of the lateral habenula (LHb) has recently been claimed to offer such an option for TRD. Rats which are bred for high susceptibility to develop learned helplessness provide a genetic model for TRD. We used the gamma-aminobutyric acid agonist muscimol to inhibit the LHb in Sprague-Dawley rats with congenital learned helplessness (cLH). Stereotactic pharmacological inhibition of the LHb exerted antidepressive effects in treatment resistant cLH rats.

MeSH terms

  • Analysis of Variance
  • Animals
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • GABA-A Receptor Agonists / pharmacology
  • GABA-A Receptor Agonists / therapeutic use
  • Habenula / drug effects*
  • Habenula / physiopathology
  • Helplessness, Learned*
  • Muscimol / pharmacology
  • Muscimol / therapeutic use*
  • Neurons / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • GABA-A Receptor Agonists
  • Muscimol