Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice

Andrew Holmes, Rebecca J. Yang, Jacqueline Crawley

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Understanding the role of neuropeptides in mediating emotional behaviors is an important avenue for discovering novel drug targets for anxiety disorders. A role for galanin in mediating anxiety-related behavior is suggested by the pattern of distribution in the CNS and the coexistence of galanin with norepinephrine in the locus coeruleus. Studies in rats have shown that central administration of galanin modulates anxiety-related behaviors, and galanin release blocks the proanxiety effects of noradrenergic activation in prestressed rats. To further investigate the role of galanin in anxiety behaviors, we conducted a comprehensive behavioral phenotyping of galanin overexpressing transgenic mice (GAL-tg). GAL-tg mice were normal on measures of general health, neurological reflexes, home cage social behaviors, sensory functions, motor coordination, and exploratory locomotor activity. In three separate tests for anxiety-related behaviors, the elevated plus-maze, light ↔ dark exploration, and open field center time, GAL-tg mice showed no anxiety-like phenotype. GAL-tg mice and wild-type littermate controls were equally responsive to the anxiolytic effects of chlordiazepoxide (10 mg/kg) in the light ↔ dark exploration test, indicating normal benzodiazepine receptor function in GAL-tg mice. Stimulation of noradrenergic cells via administration with an α2 adrenoreceptor antagonist, yohimbine (2.5 mg/kg), produced proanxiety effects in wild type mice in the light ↔ dark exploration test, but not in the GAL-tg mice. These data suggest that galanin contributes to the modulation of anxiety states induced by high levels of noradrenergic activation, but is silent under less challenging situations. A specific role for galanin in extreme anxiety states represents an attractive target for the development of novel anxiolytic treatments.

Original languageEnglish (US)
Pages (from-to)151-165
Number of pages15
JournalJournal of Molecular Neuroscience
Volume18
Issue number1-2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Galanin
Transgenic Mice
Anxiety
Phenotype
Anti-Anxiety Agents
Light
Rats
Chemical activation
Chlordiazepoxide
Locus Coeruleus
Yohimbine
Social Behavior
GABA-A Receptors
Locomotion
Anxiety Disorders
Neuropeptides
Reflex
Norepinephrine
Modulation
Health

Keywords

  • Anxiety
  • Chlordiazepoxide
  • Elevated plus-maze
  • Galanin
  • Light ↔ dark exploration test
  • Multitiered strategy
  • Norepinephrine
  • Stress
  • Transgenic mice
  • Yohimbine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice. / Holmes, Andrew; Yang, Rebecca J.; Crawley, Jacqueline.

In: Journal of Molecular Neuroscience, Vol. 18, No. 1-2, 2002, p. 151-165.

Research output: Contribution to journalArticle

@article{294f559c5ac442118cf55236d93696eb,
title = "Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice",
abstract = "Understanding the role of neuropeptides in mediating emotional behaviors is an important avenue for discovering novel drug targets for anxiety disorders. A role for galanin in mediating anxiety-related behavior is suggested by the pattern of distribution in the CNS and the coexistence of galanin with norepinephrine in the locus coeruleus. Studies in rats have shown that central administration of galanin modulates anxiety-related behaviors, and galanin release blocks the proanxiety effects of noradrenergic activation in prestressed rats. To further investigate the role of galanin in anxiety behaviors, we conducted a comprehensive behavioral phenotyping of galanin overexpressing transgenic mice (GAL-tg). GAL-tg mice were normal on measures of general health, neurological reflexes, home cage social behaviors, sensory functions, motor coordination, and exploratory locomotor activity. In three separate tests for anxiety-related behaviors, the elevated plus-maze, light ↔ dark exploration, and open field center time, GAL-tg mice showed no anxiety-like phenotype. GAL-tg mice and wild-type littermate controls were equally responsive to the anxiolytic effects of chlordiazepoxide (10 mg/kg) in the light ↔ dark exploration test, indicating normal benzodiazepine receptor function in GAL-tg mice. Stimulation of noradrenergic cells via administration with an α2 adrenoreceptor antagonist, yohimbine (2.5 mg/kg), produced proanxiety effects in wild type mice in the light ↔ dark exploration test, but not in the GAL-tg mice. These data suggest that galanin contributes to the modulation of anxiety states induced by high levels of noradrenergic activation, but is silent under less challenging situations. A specific role for galanin in extreme anxiety states represents an attractive target for the development of novel anxiolytic treatments.",
keywords = "Anxiety, Chlordiazepoxide, Elevated plus-maze, Galanin, Light ↔ dark exploration test, Multitiered strategy, Norepinephrine, Stress, Transgenic mice, Yohimbine",
author = "Andrew Holmes and Yang, {Rebecca J.} and Jacqueline Crawley",
year = "2002",
doi = "10.1385/JMN:18:1-2:151",
language = "English (US)",
volume = "18",
pages = "151--165",
journal = "Journal of Molecular Neuroscience",
issn = "0895-8696",
publisher = "Humana Press",
number = "1-2",

}

TY - JOUR

T1 - Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice

AU - Holmes, Andrew

AU - Yang, Rebecca J.

AU - Crawley, Jacqueline

PY - 2002

Y1 - 2002

N2 - Understanding the role of neuropeptides in mediating emotional behaviors is an important avenue for discovering novel drug targets for anxiety disorders. A role for galanin in mediating anxiety-related behavior is suggested by the pattern of distribution in the CNS and the coexistence of galanin with norepinephrine in the locus coeruleus. Studies in rats have shown that central administration of galanin modulates anxiety-related behaviors, and galanin release blocks the proanxiety effects of noradrenergic activation in prestressed rats. To further investigate the role of galanin in anxiety behaviors, we conducted a comprehensive behavioral phenotyping of galanin overexpressing transgenic mice (GAL-tg). GAL-tg mice were normal on measures of general health, neurological reflexes, home cage social behaviors, sensory functions, motor coordination, and exploratory locomotor activity. In three separate tests for anxiety-related behaviors, the elevated plus-maze, light ↔ dark exploration, and open field center time, GAL-tg mice showed no anxiety-like phenotype. GAL-tg mice and wild-type littermate controls were equally responsive to the anxiolytic effects of chlordiazepoxide (10 mg/kg) in the light ↔ dark exploration test, indicating normal benzodiazepine receptor function in GAL-tg mice. Stimulation of noradrenergic cells via administration with an α2 adrenoreceptor antagonist, yohimbine (2.5 mg/kg), produced proanxiety effects in wild type mice in the light ↔ dark exploration test, but not in the GAL-tg mice. These data suggest that galanin contributes to the modulation of anxiety states induced by high levels of noradrenergic activation, but is silent under less challenging situations. A specific role for galanin in extreme anxiety states represents an attractive target for the development of novel anxiolytic treatments.

AB - Understanding the role of neuropeptides in mediating emotional behaviors is an important avenue for discovering novel drug targets for anxiety disorders. A role for galanin in mediating anxiety-related behavior is suggested by the pattern of distribution in the CNS and the coexistence of galanin with norepinephrine in the locus coeruleus. Studies in rats have shown that central administration of galanin modulates anxiety-related behaviors, and galanin release blocks the proanxiety effects of noradrenergic activation in prestressed rats. To further investigate the role of galanin in anxiety behaviors, we conducted a comprehensive behavioral phenotyping of galanin overexpressing transgenic mice (GAL-tg). GAL-tg mice were normal on measures of general health, neurological reflexes, home cage social behaviors, sensory functions, motor coordination, and exploratory locomotor activity. In three separate tests for anxiety-related behaviors, the elevated plus-maze, light ↔ dark exploration, and open field center time, GAL-tg mice showed no anxiety-like phenotype. GAL-tg mice and wild-type littermate controls were equally responsive to the anxiolytic effects of chlordiazepoxide (10 mg/kg) in the light ↔ dark exploration test, indicating normal benzodiazepine receptor function in GAL-tg mice. Stimulation of noradrenergic cells via administration with an α2 adrenoreceptor antagonist, yohimbine (2.5 mg/kg), produced proanxiety effects in wild type mice in the light ↔ dark exploration test, but not in the GAL-tg mice. These data suggest that galanin contributes to the modulation of anxiety states induced by high levels of noradrenergic activation, but is silent under less challenging situations. A specific role for galanin in extreme anxiety states represents an attractive target for the development of novel anxiolytic treatments.

KW - Anxiety

KW - Chlordiazepoxide

KW - Elevated plus-maze

KW - Galanin

KW - Light ↔ dark exploration test

KW - Multitiered strategy

KW - Norepinephrine

KW - Stress

KW - Transgenic mice

KW - Yohimbine

UR - http://www.scopus.com/inward/record.url?scp=0036200155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036200155&partnerID=8YFLogxK

U2 - 10.1385/JMN:18:1-2:151

DO - 10.1385/JMN:18:1-2:151

M3 - Article

C2 - 11931346

AN - SCOPUS:0036200155

VL - 18

SP - 151

EP - 165

JO - Journal of Molecular Neuroscience

JF - Journal of Molecular Neuroscience

SN - 0895-8696

IS - 1-2

ER -