Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

Brain Res. 2006 Feb 16:1073-1074:229-39. doi: 10.1016/j.brainres.2005.12.053. Epub 2006 Jan 24.


The habenula complex modulates the activity of dopamine and serotonin systems in the brain. An important question remains whether there is a link between habenula dysfunction and monoamine-related disorders, such as schizophrenia. In this study, we describe an interaction between habenula lesions and stress that produces long-lasting effects on behavior. Mice received control lesions or bilateral electrolytic lesions of the habenula and were tested for fear-potentiated startle and freezing measures of conditioned fear. They were also tested for prepulse inhibition (PPI) and locomotor activity in the presence or absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with mixed dopamine/serotonin antagonist properties (clozapine). There were no detectable effects of habenula lesions on fear conditioning and no effects on PPI in the absence of stress. However, following conditioned fear stress, habenula-lesioned animals showed decreased PPI which normalized with clozapine. Lesioned animals also showed diminished activity at baseline, with hyperlocomotion following apomorphine. These data support the hypothesis that the habenula may be normally involved in stress-dependent regulation of monoamine systems.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Apomorphine / administration & dosage
  • Behavior, Animal
  • Dopamine / metabolism*
  • Electrolysis / adverse effects
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Fear / psychology
  • Freezing Reaction, Cataleptic / physiology
  • Habenula / injuries
  • Habenula / physiopathology*
  • Locomotion / drug effects
  • Locomotion / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition / physiology*
  • Reflex, Startle / physiology
  • Stress, Physiological / etiology
  • Stress, Physiological / physiopathology*


  • Apomorphine
  • Dopamine