Vol. 296, Issue 3, 1074-1084, March 2001

Selective Dopamine Receptor Stimulation Differentially Affects [³H]Arachidonic Acid Incorporation, a Surrogate Marker for Phospholipase A₂-Mediated Neurotransmitter Signal Transduction, in a Rodent Model of Parkinson's Disease

Takanori Hayakawa , Michael C. J. Chang, Stanley I. Rapoport and Nathan M. Appel

Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland (T.H., M.C.J.C., S.I.R., N.M.A.); Department of Neurosurgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan (T.H.); and Division of Applied Pharmacology Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, Maryland (N.M.A.)

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.