Ascending projections of the dorsal raphe nucleus to the caudate-putamen complex in rat: A degeneration and anterograde tracing study

Abstract

Studies on neuropathological processes underlying the clinical syndromes of Parkinson's disease (PD) have confirmed that PD affects both dopaminergic as well as serotonergic projections of the dorsal raphe nucleus (DRN). These projections were investigated in the present study, using neurochemical lesion and anterograde tracing techniques. One of the suggested mechanisms responsible for the progressive loss of dopamine (DA) in PD is the oxidative stress-induced degeneration. The free radical nitric oxide (NO) appears to be of special interest. The presence of this molecule in both the serotonergic and dopaminergic DRN projections to the Caudate-Putamen (CPu) was examined in the present study, using a combined neurochemical lesion technique and NADPH-d histochemistry. NO and serotonin were found to be colocalized in the dorsomedial cluster of the DRN. However, no NOS-immunohistochemistry was detected in the serotonergic raphe-striatal projections. Loss of serotonergic neurons in the ventromedial dorsal raphe resulted in a reduction of the striatal dopaminergic innervation. Degenerating serotonergic elements were observed at both ends of the nigrostriatal pathway. Furthermore, loss of DA-immunoreactivity in the DRN was observed to be concomitant with an enhanced degeneration of the raphe cells. Serotonergic raphe neurons may therefore be inhibited by dopaminergic input of the DRN originating in the substantia nigra. Loss of this inhibition might augment the hypothesized degeneration of the serotonergic raphe-striatal projections in PD. Malfunction of such a feedback system could be a possible cause of the DA deficiency in PD.