Mechanisms of hyperactivity in dopamine deficient state

2014 Fiscal Year Final Research Report

• Project/Area Number: 24650205
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: 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: ドーパミン / マウス / 運動 / アセチルコリン / 線条体

Outline of Final Research Achievements

Dopamine plays an essential role in brain functions including motor control, reward, and psychosis. Low levels of dopamine generally cause hypolocomotion as seen in Parkinson’s disease patients. Unexpectedly, dopamine-deficient 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, one of the atypical antipsychotic drugs. Among multiple actions of clozapine, muscarinic acetylcholine activation markedly reduced locomotor activity in dopamine-deficient mice. The expression of choline acetyltransferase was reduced and extracellular acetylcholine levels were significantly reduced in dopamine-deficient mice. In conclusion, these results indicate that cholinergic system may be involved in hyperactivity in dopamine-deficient mice.

Free Research Field

神経科学