Neuronal damage in antipsychotics-induced dopamine-supersensitivity-state rats: the alteration of astroglial processing and heat-shock protein HSP-70 in the striatum and hippocampus

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16664
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Chiba University
• Principal Investigator: Oda Yasunori 千葉大学, 医学部附属病院, 講師 (50770583)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ドパミン過感受性精神病 / 遅発性ジスキネジア / 神経損傷 / 抗精神病薬

Outline of Final Research Achievements

The excessive blockade of dopamine D2 receptors (DRD2s) with long-term antipsychotic treatment is known to induce a dopamine supersensitivity state (DSS). We investigated whether antipsychotic-induced neuronal damage plays a role in the development of DSS.Haloperidol (HAL; 0.75 mg/kg/day for 14 days) or vehicle was administered to rats. Haloperidol-treated rats were divided into groups of DSS rats and non-DSS rats based on their voluntary locomotion data. We then determined the tissue levels of glutamate transporter-1 (GLT-1)/glutamine synthetase (GS) and heat shock protein-70 (HSP-70) in the rats' brain regions.The levels of HSP-70 in the striatum and CA-3 region of the DSS rats were significantly higher than those of the control and non-DSS rats. These results suggest that the DSS rats experienced striatal neuronal damage and indicate that a HAL-induced upregulation of HSP-70 and the GLT-1/GS system in the CA3 may be involved in the development of DSS.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

ドパミン過感受性精神病は臨床家が治療に難渋している重篤な副作用の一つであり、その発症機序を知ることは適切な治療を考える上で非常に大切である。
ドパミン過感受性精神病の主症状の一つに遅発性ジスキネジアがあるが、遅発性ジスキネジアは統合失調症の患者さんに限らず、臨床で広く出会う治療抵抗性の副作用である。今回の我々の研究で遅発性ジスキネジアの解明に一歩近づいたと考えられる。また、今回の研究成果をもとに、今後は電気けいれん療法がこれらの神経損傷に与える影響を調べていく予定である。