The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies
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The role of serotonin (5-HT) on aggression has been extensively studied; nonetheless, the role of this neurotransmitter in aggression is still inconclusive.
The current meta-analytical review investigated the role of increased 5-HT neurotransmission in aggression.
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.
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.
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.
KeywordsSerotonin Meta-analysis Aggression Preclinical
The authors extend their special thanks to J.A. Hall for critical insight and editorial construction of this manuscript. This publication was made possible by Grant (RO1) DA10547 from NIDA to R.H.M. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIDA.
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