The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies

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#5-hydroxytryptophan #aggression #animals #antidepressive-agents-second-generation #behavior-animal

The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies

Carrillo et al., 2009 | Psychopharmacology (Berl) | Meta Analysis

Citation

Carrillo Maria, Ricci Lesley A, ... Melloni Richard H. The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies. Psychopharmacology (Berl). 2009-Aug;205(3):349-68. doi:10.1007/s00213-009-1543-2

Abstract

RATIONALE: The role of serotonin (5-HT) on aggression has been extensively studied; nonetheless, the role of this neurotransmitter in aggression is still inconclusive. OBJECTIVES: The current meta-analytical review investigated the role of increased 5-HT neurotransmission in aggression. METHODS: Preclinical studies using serotonin reuptake inhibitors, 5-hydroxytryptophan, L-tryptophan, or serotonin (5-HT) to increase 5-HT levels were included in this meta-analysis. An overall effect of serotonin on aggression was calculated, and the role of several moderator variables was analyzed. RESULTS: A total of 218 effect sizes revealed that increased 5-HT had an overall significant inhibitory effect on aggression (r = 0.3). The results showed that increased 5-HT had the strongest inhibitory effect on aggression when (1) a specific strain or species (e.g., Long Evans) was used; (2) aggression was offensive or predatory and/or induced by administration of 5,7-dihydroxytryptamine or p-chlorophenylalanine; (3) zimelidine, sertraline, L-tryptophan, citalopram, or 5-HT were used to increase 5-HT; (4) treatment was acute; (5) long chronic treatment durations were used; and (6) time between last injection and behavior testing was within 8 h before or after peak plasma concentration of drug. In contrast, the results revealed that increased-5-HT-facilitated aggression could be predicted when (1) Wistar rats, (2) social isolation or stress to induce aggression, and/or (3) animals treated for less than 3 weeks were used. CONCLUSIONS: Although 5-HT has an overall inhibitory effect on aggression, the animal's genetic background, drug, treatment time, aggression inducing paradigm, and aggression type are critical variables that influence and modify this effect.

Key Findings

A total of 218 effect sizes revealed that increased 5-HT had an overall significant inhibitory effect on aggression (r = 0.3). The results showed that increased 5-HT had the strongest inhibitory effect on aggression when (1) a specific strain or species (e.g., Long Evans) was used; (2) aggression was offensive or predatory and/or induced by administration of 5,7-dihydroxytryptamine or p-chlorophenylalanine; (3) zimelidine, sertraline, L-tryptophan, citalopram, or 5-HT were used to increase 5-HT;

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition stress

MeSH Terms

  • 5-Hydroxytryptophan
  • Aggression
  • Animals
  • Antidepressive Agents, Second-Generation
  • Behavior, Animal
  • Fluoxetine
  • Humans
  • Serotonin
  • Selective Serotonin Reuptake Inhibitors
  • Species Specificity
  • Synaptic Transmission
  • Tryptophan

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Comparative Study, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Review
  • Vertical: 5-htp

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09