The central serotoninergic system is critical for stress
responsivity
and social behavior, and its dysregulations have been centrally implicated
in virtually all neuropsychiatric disorders. Genetic serotonin depletion
animal models could provide a tool to elucidate the causes and mechanisms
of diseases and to develop new treatment approaches. Previously, mice
lacking tryptophan hydroxylase 2 (Tph2) have been developed, showing
altered behaviors and neurotransmission. However, the effect of congenital
serotonin deficiency on emotional and social behavior in rats is still
largely unknown, as are the underlying mechanisms. In this study,
we used a Tph2 knockout (Tph2–/–) male rat
model to study how the lack of serotonin in the rat brain affects
anxiety-like and social behaviors. Since oxytocin is centrally implicated
in these behaviors, we furthermore explored whether the effects of
Tph2 knockout on behavior would relate to changes in the oxytocin
system. We show that Tph2–/– rats display
reduced anxiety-like behavior and a high level of aggression in social
interactions. In addition, oxytocin receptor expression was increased
in the infralimbic and prelimbic cortices, paraventricular nucleus,
dorsal raphe nucleus, and some subregions of the hippocampus, which
was paralleled by increased levels of oxytocin in the medial frontal
cortex and paraventricular nucleus but not the dorsal raphe nucleus,
central amygdala, and hippocampus. In conclusion, our study demonstrated
reduced anxiety but exaggerated aggression in Tph2–/– male rats and reveals for the first time a potential involvement
of altered oxytocin system function. Meanwhile, the research of oxytocin
could be distinguished in almost any psychiatric disorder including
anxiety and mental disorders. This research potentially proposes a
new target for the treatment of such disorders, from a genetic serotonin
deficiency aspect.