Analyses of dopamine-independent brain functions with dopamine deficient mice.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659549
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: IKEDA Kazutaka 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 参事研究員 (60281656)
• Co-Investigator(Kenkyū-buntansha): KASAI Shinya 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (20399471) ; FUJITA Masayo 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (90415539)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 医療・福祉 / 生理活性 / 神経科学 / 脳・神経 / 薬理学

Outline of Final Research Achievements

Dopaminergic systems have been known to be involved in the regulation of locomotor activity and development of psychosis. The present study showed that dopamine-deficient (DD) mice, which had received daily L-DOPA injections, could move effectively and even be hyperactive 72 h after the last L-DOPA injection when dopamine was almost completely depleted. Such hyperactivity was ameliorated by clozapine but not haloperidol or ziprasidone. Among multiple actions of clozapine, muscarinic acetylcholine (ACh) activation markedly reduced locomotor activity in DD mice. Furthermore, the expression of choline acetyltransferase, an ACh synthase, was reduced and extracellular ACh levels were significantly reduced in DD mice. These results suggest that the cholinergic system, in addition to the dopaminergic system, may be involved in motor control, including hyperactivity and psychosis.

Free Research Field

精神神経科学