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

• Published in: Psychopharmacologia 2009-08, Vol.205 (3), p.349-368
• Main Authors: Carrillo, Maria, Ricci, Lesley A., Coppersmith, Glen A., Melloni, Richard H.
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptophan - pharmacology; Adult and adolescent clinical studies; Aggression - drug effects; Aggressiveness; Animals; Antidepressive Agents, Second-Generation - pharmacology; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Fluoxetine - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Meta-analysis; Neurosciences; Neurotransmission and behavior; Neurotransmitters; Pharmacology/Toxicology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Review; Rodents; Serotonin - physiology; Serotonin Uptake Inhibitors - pharmacology; Social behavior disorders. Criminal behavior. Delinquency; Species Specificity; Synaptic Transmission - drug effects; Systematic review; Tryptophan - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1543-2

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.