Abstract
Our laboratory has developed a technique whereby radiolabeled long-chain fatty acids are injected intravenously in awake rats to pulse-label brain lipids, mainly phospholipids, to measure regional brain lipid metabolism by autoradiography. The brain incorporation of [3H]arachidonic acid ([3H]AA), a polyunsaturated fatty acid, may reflect regional changes in neurotransmitter signal transduction using phospholipase A2. Using this radiotracer, we examined the brain dopamine system in rats with a chronic unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta, a model of Parkinson's disease. Four weeks after lesioning, rats received either vehicle; SKF38393 or quinpirole (LY-171,555) (D1- and D2-dopamine-like agonists, respectively); or (+)-butaclamol (D1/D2 antagonist) followed by either vehicle, SKF38393, or quinpirole. They then were infused with [3H]AA and their brains processed for autoradiography. SKF38393 increased [3H]AA incorporation into the lesioned side compared with the intact side in the caudate putamen, somatosensory and motor cortices and subthalamic nucleus, but decreased incorporation in the ipsilateral ventrolateral thalamus. Quinpirole increased ipsilateral [3H]AA incorporation in the caudate putamen and somatosensory and motor cortices, and decreased it in the ventrolateral thalamus. (+)-Butaclamol blocked this effect. The data suggest up-regulation in basal ganglia and cortical dopamine circuits mediated by phospholipase A2 ipsilateral to the substantia nigra lesion.
Footnotes
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Send reprint requests to: Nathan M. Appel, Ph.D., Division of Treatment Research and Development, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd., Room 4123, MSC 9551, Bethesda, MD 20892-9551. E-mail:an69k{at}nih.gov
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These studies were carried out under the authority of a memorandum of understanding between the United States National Institutes of Health and Food and Drug Administration.
- Abbreviations:
- rCMRglc
- regional cerebral metabolic rates for glucose
- 2DG
- 2-deoxy-d-glucose
- PLA2
- phospholipase A2
- 6-OHDA
- 6-hydroxydopamine
- AA
- arachidonic acid
- GABA
- γ-aminobutyric acid
- Received September 12, 2000.
- Accepted November 29, 2000.
- U.S. Government
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