title: The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies.
abstract: 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.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, Northeastern University, 125 Nightingale Hall, 360 Huntington Avenue, Boston, MA 02155, USA. carrillo.m@neu.edu
authors.forename: Maria
authors.initials: M
authors.lastname: Carrillo
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Ricci
authors.forename: Glen A
authors.initials: GA
authors.lastname: Coppersmith
authors.forename: Richard H
authors.initials: RH
authors.lastname: Melloni
mesh_terms: 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
chemical_list: D006916:5-Hydroxytryptophan; D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan