title: Therapeutic effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice.
abstract: In patients with dementia including Alzheimer's disease, hallucinations, agitation/aggression and irritability are known to frequently occur and as distressing behavioral and psychological symptoms of dementia (BPSD). On the basis of the evidence on clinical efficacy and safety of Yokukansan, a traditional Japanese herbal medicine, on BPSD, in the present study, Yokukansan was examined in the therapeutic effects on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice. Yokukansan was p.o. administered for 7 days as a drinking water to isolated mice fed a zinc-deficient diet for 10 days, which exhibited aggressive behavior, and isolated pair-fed mice fed a control diet of the amount consumed by zinc-deficient mice for 10 days, which exhibited aggressive behavior. Aggressive behavior was evaluated by the resident-intruder test. Yokukansan (312 mg/kg/day) attenuated both aggressive behaviors of zinc-deficient and pair-fed mice. Because Yokukansan can suppress abnormal glutamatergic neuron activity, MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, and aminooxyacetic acid (AOAA), a γ-amino butyric acid (GABA) transaminase blocker, were also examined in the effects on social isolation-induced aggressive behavior. MK-801 (0.1 mg/kg) or AOAA (23 mg/kg) was i.p. injected into isolated aggressive mice. Thirty minutes later, the resident-intruder test was performed to evaluate the effect of the drugs. Both drugs attenuated aggressive behavior of zinc deficient mice, but not that of pair-fed mice. These results suggest that Yokukansan ameliorates social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice through the action against glutamatergic neurotransmitter system and other neurotransmitter systems.
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE, 52-1 Yada, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Haruka
authors.initials: H
authors.lastname: Iwaki
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ide
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D000625:Aminooxyacetic Acid / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D018682:GABA Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011930:Reaction Time / Q000187:drug effects; D012934:Social Isolation; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology; D015032:Zinc / Q000172:deficiency*
chemical_list: D004365:Drugs, Chinese Herbal; D018682:GABA Agents; D018696:Neuroprotective Agents; C524644:Yi-Gan San; D000625:Aminooxyacetic Acid; D016291:Dizocilpine Maleate; D015032:Zinc