Serotonin Depletion-Induced Maladaptive Aggression Requires the Presence of Androgens
Journal article, 2015

The sex hormone testosterone and the neurotransmitter serotonin exert opposite effects on several aspects of behavior including territorial aggression. It is however not settled if testosterone exerts its pro-aggressive effects by reducing serotonin transmission and/or if the anti-aggressive effect of serotonin requires the presence of the androgen. Using the resident intruder test, we now show that administration of the serotonin synthesis inhibitor parachlorophenylalanine (300 mg/kg x 3 days) increases the total time of attack as well as the percentage amount of social behavior spent on attack but not that spent on threat - i.e. that it induces a pattern of unrestricted, maladaptive aggression - in gonadectomized C57Bl/6 male mice receiving testosterone replacement; in contrast, it failed to reinstate aggression in those not given testosterone. Whereas these results suggest the pro-aggressive effect of testosterone to be independent of serotonin, and not caused by an inhibition of serotonergic activity, the pCPA-induced induction of maladaptive aggression appears to require the presence of the hormone. In line with these findings, pCPA enhanced the total time of attack as well the relative time spent on attacks but not threats also in wild-type gonadally intact male C57Bl/6 mice, but failed to reinstate aggression in mice rendered hypo-aggressive by early knock-out of androgen receptors in the brain (AR(NesDel) mice). We conclude that androgenic deficiency does not dampen aggression by unleashing an anti-aggressive serotonergic influence; instead serotonin seems to modulate aggressive behavior by exerting a parallel-coupled inhibitory role on androgen-driven aggression, which is irrelevant in the absence of the hormone, and the arresting of which leads to enhanced maladaptive aggression.

Author

Erik Studer

University of Gothenburg

Jakob Näslund

University of Gothenburg

Erik Andersson

University of Gothenburg

Staffan Nilsson

University of Gothenburg

Chalmers, Mathematical Sciences, Mathematical Statistics

Lars Westberg

University of Gothenburg

Elias Eriksson

University of Gothenburg

PLoS ONE

1932-6203 (ISSN) 19326203 (eISSN)

Vol. 10 5 0126462

Subject Categories

Pharmacology and Toxicology

DOI

10.1371/journal.pone.0126462

Related datasets

Data from: Serotonin depletion-induced maladaptive aggression requires the presence of androgens [dataset]

DOI: 10.5061/dryad.b4d70

More information

Latest update

9/21/2023