Sansoninto, a traditional herbal medicine, attenuates aggressive behavior and regulates serotonergic and dopaminergic systems in hypothalamus of social isolation-reared mice

抄録

[Background] Aggressive behaviors are serious problems among numerous neurological conditions including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), schizophrenia, borderline personality disorder, Huntington disease and Alzheimer's disease. Antipsychotics are used to suppress aggressive behavior. However, treatment with antipsychotic drugs is limited to some patients due to some adverse effects such as sedation and weight gain. Sansoninto (SAT), a traditional herbal medicine, is prescribed for patients feeling weakness and fatigue, annoyance, insomnia, and/or neurotic symptoms. In this study, effect of SAT on social isolation (SI)-induced aggressive behavior was examined.

　[Methods] Five-week-old mice were socially isolated for 6 weeks. Daily SAT administration (1000 mg/kg/day, p.o.) was started at 4 weeks after starting SI. Group-housed (GH) mice were used as control. To analyze aggressive behavior, each SI or GH mouse was placed individually in a neutral arena and then docile stimulus mouse was introduced into the arena. The number of attacks against docile stimulus mice was evaluated. After aggression test, mice were scarified and then analyzed the monoamine contents in hypothalamus using a HPLC-ECD system.

　[Results] SI mice showed the increased number of attacks compared with GH mice. SAT ameliorated the increased number of attacks in SI mice. The levels of dopamine (DA) and DOPAC were not different in all groups (GH mice, vehicle-treated SI mice, SAT-treated SI mice). But SAT-treated SI mice showed significant increase in HVA levels, resulting in increased DA turnover rate (HVA/DA) compared with vehicle-treated SI mice. The levels of tryptophan, 5-HT and 5-HIAA were not different in all groups. But SAT-treated SI mice showed increased tryptophan turnover rate (5-HT/tryptophan) compared with vehicle-treated SI mice.

　[Conclusions] These results suggest that SAT attenuates postsynaptic D2 mechanism by decrease of synaptic DA levels and enhances postsynaptic 5-HT mechanism by increase of synaptic 5-HT levels. This regulation of dopaminergic and serotonergic system in hypothalamus could result in suppression of aggressive behavior. SAT might be useful for patients with aggression in various mental illnesses.