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Neuroimage. 2007 Oct 1;37(4):1112-21. Epub 2007 Jun 27.

In vivo imaging of disturbed pre- and post-synaptic dopaminergic signaling via arachidonic acid in a rat model of Parkinson's disease.

Author information

  • 1Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg. 9, Room 1S126, Bethesda, MD 20892, USA. abesh@mail.nih.gov

Abstract

BACKGROUND:

Parkinson's disease involves loss of dopamine (DA)-producing neurons in the substantia nigra, associated with fewer pre-synaptic DA transporters (DATs) but more post-synaptic dopaminergic D2 receptors in terminal areas of these neurons.

HYPOTHESIS:

Arachidonic acid (AA) signaling via post-synaptic D2 receptors coupled to cytosolic phospholipase A2 (cPLA2) will be reduced in terminal areas ipsilateral to a chronic unilateral substantia nigra lesion in rats given D-amphetamine, which reverses the direction of the DAT, but will be increased in rats given quinpirole, a D2-receptor agonist.

METHODS:

D-amphetamine (5.0 mg/kg i.p.), quinpirole (1.0 mg/kg i.v.), or saline was administered to unanesthetized rats having a chronic unilateral lesion of the substantia nigra. AA incorporation coefficients, k* (radioactivity/integrated plasma radioactivity), markers of AA signaling, were measured using quantitative autoradiography in 62 bilateral brain regions following intravenous [1-(14)C]AA.

RESULTS:

In rats given saline (baseline), k* was elevated in 13 regions in the lesioned compared with intact hemisphere. Quinpirole increased k* in frontal cortical and basal ganglia regions bilaterally, more so in the lesioned than intact hemisphere. D-amphetamine increased k* bilaterally but less so in the lesioned hemisphere.

CONCLUSIONS:

Increased baseline elevations of k* and increased responsiveness to quinpirole in the lesioned hemisphere are consistent with their higher D2-receptor and cPLA2 activity levels, whereas reduced responsiveness to D-amphetamine is consistent with dropout of pre-synaptic elements containing the DAT. In vivo imaging of AA signaling using dopaminergic drugs can identify pre- and post-synaptic DA changes in animal models of Parkinson's disease.

PMID:
17681816
[PubMed - indexed for MEDLINE]
PMCID:
PMC2040339
Free PMC Article
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