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.
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 [(3)H]arachidonic acid ([(3)H]AA), a polyunsaturated fatty acid, may reflect regional changes in neurotransmitter signal transduction using phospholipase A(2). 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) (D(1)- and D(2)-dopamine-like agonists, respectively); or (+)-butaclamol (D(1)/D(2) antagonist) followed by either vehicle, SKF38393, or quinpirole. They then were infused with [(3)H]AA and their brains processed for autoradiography. SKF38393 increased [(3)H]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 [(3)H]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 A(2) ipsilateral to the substantia nigra lesion.
Hayakawa
T
T
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chang
M C
MC
Rapoport
S I
SI
Appel
N M
NM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction; D014316:Tritium
D015415:Biomarkers; D018491:Dopamine Agonists; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D016718:Arachidonic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D010741:Phospholipases A; D054467:Phospholipases A2