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

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 para-chlorophenylalanine (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 (ARNesDel 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.

性激素睾酮（testosterone）与神经递质血清素（serotonin）在包括领地攻击在内的多种行为维度上发挥着相反的调控作用。然而目前尚无定论：睾酮的促攻击效应是否通过削弱血清素传递实现，亦或是血清素的抗攻击效应是否依赖于雄激素的存在。本研究采用居住者-入侵者攻击实验（resident intruder test）证实：给予血清素合成抑制剂对氯苯丙氨酸（para-chlorophenylalanine，后文简称pCPA），以300mg/kg的剂量连续给药3天，可在接受睾酮替代治疗的去势C57BL/6雄性小鼠中，延长攻击总时长并提升攻击行为占社交行为的百分比，但不影响威胁行为占比——即诱导出无限制的适应不良攻击行为模式；与之相反，该抑制剂无法在未接受睾酮给药的小鼠中恢复攻击行为。上述结果表明，睾酮的促攻击效应不依赖于血清素，并非通过抑制血清素能活性实现；但pCPA诱导的适应不良攻击行为似乎需要雄激素的存在。与上述发现一致的是，pCPA同样可在性腺完整的野生型C57BL/6雄性小鼠中延长攻击总时长并提升攻击行为的相对占比，却不影响威胁行为占比；但该抑制剂无法在脑内雄激素受体（androgen receptor）早期敲除的低攻击性小鼠（ARNesDel小鼠）中恢复攻击行为。本研究最终得出结论：雄激素缺乏并非通过解除血清素的抗攻击调控作用来削弱攻击行为；相反，血清素似乎通过对雄激素介导的攻击行为发挥平行偶联的抑制作用来调控攻击行为——该调控作用在雄激素缺失时不发挥功能，阻断该抑制作用则会加剧适应不良的攻击行为。