THE DEVELOPMENT OF STRIATAL PATCH MATRIX ORGANIZATION AFTER PRENATAL METHYLAZOXYMETHANOL - A COMBINED IMMUNOCYTOCHEMICAL AND BROMO-DEOXY-URIDINE BIRTHDATING STUDY

The antimitotic drug methylazoxymethanol was used to destroy striatal patch neurons during their three-day-period of neurogenesis in the rat . Single or multiple injections of methylazoxymethanol were given duri ng embryonic days 13-15, the period when patch neurons are known to un dergo their final cell division. Methylazoxymethanol treatments produc ed a dramatic reduction in striatal volume. Immunocytochemical analysi s revealed the continued presence of patches of neurons that were subs tance P-immunoreactive and devoid of calbindin and enkephalin immunore activity. Both the number of patches and relative Volume occupied by p atches was reduced in methylazoxymelhanol-treated striata. Patch neuro ns could also be labelled by an intrastriatal injection of FluoroGold during the first postnatal week. The early ingrowth of nigrostriatal d opamine afferents was less noticeably patchy in the methylazoxymethano l-treated animals, in part owing to an overall increase in density. La rge reductions in the number of neurons immunoreactive for choline ace tyltransferase were observed, whereas NADPH diaphorase-stained neurons were not reduced unless methylazoxymethanol was given on embryonic da y 15, Injections of bromo-deoxy-uridine, either during or after the 24 h that each methylazoxymethanol injection was considered to be effect ive, revealed that (i) some patch neurons continued to be generated in the 24-h period following methylazoxymethanol administration, and (ii ) many patch neurons were generated after the effects of methylazoxyme thanol had worn off.These findings demonstrate that it was impossible to completely eliminate the patches using methylazoxymethanol injectio ns during the period of patch neurogenesis. However, methylazoxymethan ol treatment during this time did produce a dramatic loss of cells and a relatively greater reduction in patch volume. Despite this disrupti on, the appropriate compartmentalization of neuroactive substances app eared to be maintained.