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

Scott Heldt, Kerry J. Ressler

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)229-239
Number of pages11
JournalBrain Research
Volume1073-1074
Issue number1
DOIs
StatePublished - Feb 16 2006

Fingerprint

Habenula
Locomotion
Dopamine
Fear
Apomorphine
Clozapine
Serotonin Antagonists
Dopamine Antagonists
Dopamine Agonists
Prepulse Inhibition
Freezing
Antipsychotic Agents
Serotonin
Schizophrenia
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion. / Heldt, Scott; Ressler, Kerry J.

In: Brain Research, Vol. 1073-1074, No. 1, 16.02.2006, p. 229-239.

Research output: Contribution to journalArticle

Heldt, Scott ; Ressler, Kerry J. / Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion. In: Brain Research. 2006 ; Vol. 1073-1074, No. 1. pp. 229-239.
@article{e95f4b323e694fc7bb7a2676c4f815ce,
title = "Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion",
abstract = "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.",
author = "Scott Heldt and Ressler, {Kerry J.}",
year = "2006",
month = "2",
day = "16",
doi = "10.1016/j.brainres.2005.12.053",
language = "English (US)",
volume = "1073-1074",
pages = "229--239",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

AU - Heldt, Scott

AU - Ressler, Kerry J.

PY - 2006/2/16

Y1 - 2006/2/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33644935419&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644935419&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2005.12.053

DO - 10.1016/j.brainres.2005.12.053

M3 - Article

C2 - 16442084

AN - SCOPUS:33644935419

VL - 1073-1074

SP - 229

EP - 239

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -