Reduced aggression in mice lacking the serotonin transporter

Andrew Holmes, Dennis L. Murphy, Jacqueline Crawley

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Rationale: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. Objectives: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT1A/1B receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. Methods: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT1A/1B receptor function was assessed via the pharmacological effects of the 5-HT1A/1B receptor agonist, RU24969, on locomotion. Results: 5-HTT -/- mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/- and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/- and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and +/+, but not 5-HTT -/- mice. Conclusions: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT1A/1B receptor function may contribute to reduced aggression in 5-HTT KO mice.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalPsychopharmacology
Volume161
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Aggression
Receptor, Serotonin, 5-HT1A
Knockout Mice
Locomotion
Violence
Serotonin
Pharmacology
Phenotype
Brain

Keywords

  • Aggression
  • Knockout mouse
  • Locomotor activity
  • Resident-intruder
  • RU24969
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology

Cite this

Reduced aggression in mice lacking the serotonin transporter. / Holmes, Andrew; Murphy, Dennis L.; Crawley, Jacqueline.

In: Psychopharmacology, Vol. 161, No. 2, 2002, p. 160-167.

Research output: Contribution to journalArticle

Holmes, Andrew ; Murphy, Dennis L. ; Crawley, Jacqueline. / Reduced aggression in mice lacking the serotonin transporter. In: Psychopharmacology. 2002 ; Vol. 161, No. 2. pp. 160-167.
@article{40c2be5c6cad4df28faec002c8bb855b,
title = "Reduced aggression in mice lacking the serotonin transporter",
abstract = "Rationale: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. Objectives: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT1A/1B receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. Methods: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT1A/1B receptor function was assessed via the pharmacological effects of the 5-HT1A/1B receptor agonist, RU24969, on locomotion. Results: 5-HTT -/- mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/- and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/- and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and +/+, but not 5-HTT -/- mice. Conclusions: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT1A/1B receptor function may contribute to reduced aggression in 5-HTT KO mice.",
keywords = "Aggression, Knockout mouse, Locomotor activity, Resident-intruder, RU24969, Serotonin transporter",
author = "Andrew Holmes and Murphy, {Dennis L.} and Jacqueline Crawley",
year = "2002",
doi = "10.1007/s00213-002-1024-3",
language = "English (US)",
volume = "161",
pages = "160--167",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Reduced aggression in mice lacking the serotonin transporter

AU - Holmes, Andrew

AU - Murphy, Dennis L.

AU - Crawley, Jacqueline

PY - 2002

Y1 - 2002

N2 - Rationale: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. Objectives: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT1A/1B receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. Methods: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT1A/1B receptor function was assessed via the pharmacological effects of the 5-HT1A/1B receptor agonist, RU24969, on locomotion. Results: 5-HTT -/- mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/- and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/- and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and +/+, but not 5-HTT -/- mice. Conclusions: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT1A/1B receptor function may contribute to reduced aggression in 5-HTT KO mice.

AB - Rationale: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. Objectives: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT1A/1B receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. Methods: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT1A/1B receptor function was assessed via the pharmacological effects of the 5-HT1A/1B receptor agonist, RU24969, on locomotion. Results: 5-HTT -/- mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/- and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/- and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and +/+, but not 5-HTT -/- mice. Conclusions: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT1A/1B receptor function may contribute to reduced aggression in 5-HTT KO mice.

KW - Aggression

KW - Knockout mouse

KW - Locomotor activity

KW - Resident-intruder

KW - RU24969

KW - Serotonin transporter

UR - http://www.scopus.com/inward/record.url?scp=0036250544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036250544&partnerID=8YFLogxK

U2 - 10.1007/s00213-002-1024-3

DO - 10.1007/s00213-002-1024-3

M3 - Article

VL - 161

SP - 160

EP - 167

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 2

ER -