Partial preservation of motor function by inhibition of arachidonate metabolism in rats with phospholipase A2-induced caudate lesions.
Dexamethasone pretreatment prevents motor impairment manifested by ipsilateral rotation and phospholipid alterations resulting from phospholipase A2-induced caudate nucleus lesions in rats. If motor function preservation is attributed solely to the antiprostaglandin activity of dexamethasone, then indomethacin (an inhibitor of cyclooxygenase) and phenidone (an inhibitor of both lipoxygenase and cyclooxygenase) should also diminish rotation. Phenidone offered dose-related, partial protection whereas indomethacin did not. Histologic sections of rat brain indicated that a positive correlation existed between the size of the caudate lesion and number of rotations for the various treatments. Because dexamethasone produced essentially complete protection, it is hypothesized that dexamethasone protects caudate motor function by interfering with breakdown of membrane phospholipids, as well as by preventing formation of arachidonate and its products.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D011720:Pyrazoles; D016718:Arachidonic Acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; C015429:phenidone; D007213:Indomethacin