Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior

Andrew Holmes, Qian Li, Elizabeth A. Koenig, Eric Gold, Dejaimenay Stephenson, Rebecca J. Yang, Jennifer Dreiling, Tim Sullivan, Jacqueline Crawley

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Rationale: Galanin and its receptors exert inhibitory neuromodulatory control over brain monoamines. Rat studies revealed that galanin expression is upregulated by exposure to stressors and that galanin manipulations modify neuroendocrine and behavioral responses to stress, leading to the hypothesis that galanin mediates depression-related behaviors. Methods: In the present study, we examined the role of galanin in modulating antidepressant-related behavior in galanin overexpressing transgenic (GAL-tg) mice and galanin receptor R1 knockout (GAL-R1 KO) mice, using the tail suspension test (TST). Quantitative autoradiography for 5-HT1A-R and serotonin transporter binding density tested for changes in these two major regulatory components of the 5-HT system in galanin mutant mice. Results: Baseline TST behavior was normal in GAL-tg and GAL-R1 KO mice, and intracerebroventricular administration of galanin failed to alter TST behavior in normal C57BL/6J mice. The TST anti-immobility effects of acute treatment with the serotonin reuptake inhibitor, fluoxetine (0-30 mg/kg), and the norepinephrine reuptake inhibitor, desipramine (0-30 mg/kg), were unaltered in galanin mutant mice. Hippocampal 5-HT1A-R density was significantly elevated in GAL-tg and GAL-R1 KO mice, while hippocampal 5-HTT density was reduced in GAL-R1 KO mice, relative to controls. Conclusion: Neither pharmacological nor molecular genetic manipulations of galanin altered depression-related profiles in the TST. Possible functional alterations in hippocampal 5-HT neurotransmission may have contributed to these negative results. These preliminary findings provide evidence against the hypothesis that galanin plays a central role in mouse depression-related behaviors. It remains possible that galanin modulates depression-related responses in other experimental paradigms and species.

Original languageEnglish (US)
Pages (from-to)276-285
Number of pages10
JournalPsychopharmacology
Volume178
Issue number2-3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

Galanin Receptors
Hindlimb Suspension
Galanin
Knockout Mice
Depression
Serotonin
Serotonin Plasma Membrane Transport Proteins
Desipramine
Fluoxetine
Serotonin Uptake Inhibitors

Keywords

  • Antidepressant
  • Autoradiography
  • Behavior
  • Depression
  • Galanin
  • Knockout
  • Mouse
  • Norepinephrine
  • Serotonin
  • Stress

ASJC Scopus subject areas

  • Pharmacology

Cite this

Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior. / Holmes, Andrew; Li, Qian; Koenig, Elizabeth A.; Gold, Eric; Stephenson, Dejaimenay; Yang, Rebecca J.; Dreiling, Jennifer; Sullivan, Tim; Crawley, Jacqueline.

In: Psychopharmacology, Vol. 178, No. 2-3, 03.2005, p. 276-285.

Research output: Contribution to journalArticle

Holmes, Andrew ; Li, Qian ; Koenig, Elizabeth A. ; Gold, Eric ; Stephenson, Dejaimenay ; Yang, Rebecca J. ; Dreiling, Jennifer ; Sullivan, Tim ; Crawley, Jacqueline. / Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior. In: Psychopharmacology. 2005 ; Vol. 178, No. 2-3. pp. 276-285.
@article{48d0ca0f5d7b4c1fa494ced6c954b70d,
title = "Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior",
abstract = "Rationale: Galanin and its receptors exert inhibitory neuromodulatory control over brain monoamines. Rat studies revealed that galanin expression is upregulated by exposure to stressors and that galanin manipulations modify neuroendocrine and behavioral responses to stress, leading to the hypothesis that galanin mediates depression-related behaviors. Methods: In the present study, we examined the role of galanin in modulating antidepressant-related behavior in galanin overexpressing transgenic (GAL-tg) mice and galanin receptor R1 knockout (GAL-R1 KO) mice, using the tail suspension test (TST). Quantitative autoradiography for 5-HT1A-R and serotonin transporter binding density tested for changes in these two major regulatory components of the 5-HT system in galanin mutant mice. Results: Baseline TST behavior was normal in GAL-tg and GAL-R1 KO mice, and intracerebroventricular administration of galanin failed to alter TST behavior in normal C57BL/6J mice. The TST anti-immobility effects of acute treatment with the serotonin reuptake inhibitor, fluoxetine (0-30 mg/kg), and the norepinephrine reuptake inhibitor, desipramine (0-30 mg/kg), were unaltered in galanin mutant mice. Hippocampal 5-HT1A-R density was significantly elevated in GAL-tg and GAL-R1 KO mice, while hippocampal 5-HTT density was reduced in GAL-R1 KO mice, relative to controls. Conclusion: Neither pharmacological nor molecular genetic manipulations of galanin altered depression-related profiles in the TST. Possible functional alterations in hippocampal 5-HT neurotransmission may have contributed to these negative results. These preliminary findings provide evidence against the hypothesis that galanin plays a central role in mouse depression-related behaviors. It remains possible that galanin modulates depression-related responses in other experimental paradigms and species.",
keywords = "Antidepressant, Autoradiography, Behavior, Depression, Galanin, Knockout, Mouse, Norepinephrine, Serotonin, Stress",
author = "Andrew Holmes and Qian Li and Koenig, {Elizabeth A.} and Eric Gold and Dejaimenay Stephenson and Yang, {Rebecca J.} and Jennifer Dreiling and Tim Sullivan and Jacqueline Crawley",
year = "2005",
month = "3",
doi = "10.1007/s00213-004-1997-1",
language = "English (US)",
volume = "178",
pages = "276--285",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "2-3",

}

TY - JOUR

T1 - Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior

AU - Holmes, Andrew

AU - Li, Qian

AU - Koenig, Elizabeth A.

AU - Gold, Eric

AU - Stephenson, Dejaimenay

AU - Yang, Rebecca J.

AU - Dreiling, Jennifer

AU - Sullivan, Tim

AU - Crawley, Jacqueline

PY - 2005/3

Y1 - 2005/3

N2 - Rationale: Galanin and its receptors exert inhibitory neuromodulatory control over brain monoamines. Rat studies revealed that galanin expression is upregulated by exposure to stressors and that galanin manipulations modify neuroendocrine and behavioral responses to stress, leading to the hypothesis that galanin mediates depression-related behaviors. Methods: In the present study, we examined the role of galanin in modulating antidepressant-related behavior in galanin overexpressing transgenic (GAL-tg) mice and galanin receptor R1 knockout (GAL-R1 KO) mice, using the tail suspension test (TST). Quantitative autoradiography for 5-HT1A-R and serotonin transporter binding density tested for changes in these two major regulatory components of the 5-HT system in galanin mutant mice. Results: Baseline TST behavior was normal in GAL-tg and GAL-R1 KO mice, and intracerebroventricular administration of galanin failed to alter TST behavior in normal C57BL/6J mice. The TST anti-immobility effects of acute treatment with the serotonin reuptake inhibitor, fluoxetine (0-30 mg/kg), and the norepinephrine reuptake inhibitor, desipramine (0-30 mg/kg), were unaltered in galanin mutant mice. Hippocampal 5-HT1A-R density was significantly elevated in GAL-tg and GAL-R1 KO mice, while hippocampal 5-HTT density was reduced in GAL-R1 KO mice, relative to controls. Conclusion: Neither pharmacological nor molecular genetic manipulations of galanin altered depression-related profiles in the TST. Possible functional alterations in hippocampal 5-HT neurotransmission may have contributed to these negative results. These preliminary findings provide evidence against the hypothesis that galanin plays a central role in mouse depression-related behaviors. It remains possible that galanin modulates depression-related responses in other experimental paradigms and species.

AB - Rationale: Galanin and its receptors exert inhibitory neuromodulatory control over brain monoamines. Rat studies revealed that galanin expression is upregulated by exposure to stressors and that galanin manipulations modify neuroendocrine and behavioral responses to stress, leading to the hypothesis that galanin mediates depression-related behaviors. Methods: In the present study, we examined the role of galanin in modulating antidepressant-related behavior in galanin overexpressing transgenic (GAL-tg) mice and galanin receptor R1 knockout (GAL-R1 KO) mice, using the tail suspension test (TST). Quantitative autoradiography for 5-HT1A-R and serotonin transporter binding density tested for changes in these two major regulatory components of the 5-HT system in galanin mutant mice. Results: Baseline TST behavior was normal in GAL-tg and GAL-R1 KO mice, and intracerebroventricular administration of galanin failed to alter TST behavior in normal C57BL/6J mice. The TST anti-immobility effects of acute treatment with the serotonin reuptake inhibitor, fluoxetine (0-30 mg/kg), and the norepinephrine reuptake inhibitor, desipramine (0-30 mg/kg), were unaltered in galanin mutant mice. Hippocampal 5-HT1A-R density was significantly elevated in GAL-tg and GAL-R1 KO mice, while hippocampal 5-HTT density was reduced in GAL-R1 KO mice, relative to controls. Conclusion: Neither pharmacological nor molecular genetic manipulations of galanin altered depression-related profiles in the TST. Possible functional alterations in hippocampal 5-HT neurotransmission may have contributed to these negative results. These preliminary findings provide evidence against the hypothesis that galanin plays a central role in mouse depression-related behaviors. It remains possible that galanin modulates depression-related responses in other experimental paradigms and species.

KW - Antidepressant

KW - Autoradiography

KW - Behavior

KW - Depression

KW - Galanin

KW - Knockout

KW - Mouse

KW - Norepinephrine

KW - Serotonin

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=15044341571&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15044341571&partnerID=8YFLogxK

U2 - 10.1007/s00213-004-1997-1

DO - 10.1007/s00213-004-1997-1

M3 - Article

C2 - 15365683

AN - SCOPUS:15044341571

VL - 178

SP - 276

EP - 285

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 2-3

ER -