Effect of imipramine on 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in rat striatum

We examined the effect of imipramine (a tricyclic antidepressant drug) on hydroxyl radical (.OH) generation induced by 1-methyl-4-phenylpyridinium ion (MPP+) in extracellular fluid of rat striatum, using a microdialysis technique. Imipramine enhanced the formation of .OH trapped as 2,3-dihydroxybenzoic acid (DHBA) induced by MPP+ (5 mM). Introduction of imipramine (0.1, 0.5 and 1.0 mM) dose-dependently increased the level of dopamine (DA) release. Concomitantly, imipramine enhanced DA efflux and the level of DHBA induced by MPP+, as compared with MPP+-treated control. When corresponding experiments were performed with reserpinized rats, there were small increases in the levels of DA and nonsignificant increase in the formation of DHBA. When iron (11) was administered to imipramine (I mM)-treated animals, a marked elevation of DHBA was observed, compared with MPP+-only treated animals. A positive linear correlation was observed between iron (11) and DHBA (R-2=0.985) in the dialysate. These results indicate that imipramine enhances generation of .OH induced by MPP+ during enhanced DA overflow. (C) 2002 Elsevier Science B.V. All rights reserved.