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 language | English (US) |
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Pages (from-to) | 160-167 |
Number of pages | 8 |
Journal | Psychopharmacology |
Volume | 161 |
Issue number | 2 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- Aggression
- Knockout mouse
- Locomotor activity
- Resident-intruder
- RU24969
- Serotonin transporter
ASJC Scopus subject areas
- Pharmacology