The effects ofN-methyl- d-aspartate and kainate lesions of the rat striatum on striatal ornithine decar☐ylase activity and polyamine levels

Abstract

The intrastriatal injection ofN-methyl- d-aspartate (NMDA) (250 nmol) produced a delayed and marked increase in striatal ornithine decar☐ylase (ODC) activity and putrescine levels which peaked 6–15 h following the injection of NMDA. Striatal ODC activity subsequently returned to normal values while putrescine levels remained significantly elevated for up to 4 days following the lesion. NMDA produced an early and progressive decline in striatal spermine and spermidine levels, preceding the increase in ODC activity, with a maximum effect 2 h following injection. Spermidine levels returned to normal 6 h post-NMDA infusion, and subsequently increased to above normal levels 36 h and 4 days after the infusion of NMDA. This late increase in striatal spermidine levels paralleled an increase in the binding of the glial cell/macrophage marker [ 3H]PK 11195. Spermine levels tended to return to normal values 6 h after the injection of NMDA but may be further depressed at later intervals (15 h to 4 days). The intrastriatal injection of saline also resulted in a delayed increase in striatal ODC activity and putrescine levels, but these changes were minor compared to those produced by NMDA. Intrastriatal saline injection provoked no consistent change in striatal spermine or spermidine levels. The changes in polyamine metabolism produced by the instriatal injection of kainic acid (4 nmol) were only analysed at 6 and 15 h following injection but were qualitatively similar to those produced by NMDA although perhaps following a slightly more delayed time-course. Neurotoxic lesions of the striatum thus provoke changes in ODC activity and increased levels of putrescine that follow closely the time-course of similar events in the ischaemic brain. The initial early changes in spermine and spermidine levels induced by NMDA could perhaps alter the functioning of the NMDA receptor itself via its polyamine-sensitive modulatory site and contribute to a feed-forward activation of NMDA receptors and prolonged NMDA receptor-mediated toxicity.