The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies.
BACKGROUND
The role of serotonin (5-HT) on aggression has been extensively studied; nonetheless, the role of this neurotransmitter in aggression is still inconclusive.


OBJECTIVE
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.
Carrillo
Maria
M
Behavioral Neuroscience Program, Department of Psychology, Northeastern University, 125 Nightingale Hall, 360 Huntington Avenue, Boston, MA 02155, USA. carrillo.m@neu.edu
Ricci
Lesley A
LA
Coppersmith
Glen A
GA
Melloni
Richard H
RH
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000374:Aggression / Q000187:drug effects*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013045:Species Specificity; D009435:Synaptic Transmission / Q000187:drug effects*; D014364:Tryptophan / Q000494:pharmacology
D006916:5-Hydroxytryptophan; D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan