Opposite changes in striatal neuropeptide Y immunoreactivity after partial and complete serotonergic depletion in the...

The aim of this study was to investigate the consequences of partial vs. complete serotonergic (5-HT) depletions on the immunoreactivity of striatal interneurons containing neuropeptide Y (NPY). Taking into account the plasticity of the monoaminergic neurons, the effects of various doses of 5,7-dihydroxytryptamine (5,7-DHT) injected into the anterior raphe nuclei and P-chlorophenylalanine (PCPA) administration were compared in the dorsal (caudate-putamen) and the ventral (nucleus accumbens) striatum. Twenty days after administering 5,7-DHT injections inducing a substantial but partial decrease in the striatal 5-HT concentrations (about 80%), we detected a significant decrease in the number of NPY immunoreactive cells. In contrast, the PCPA inhibition of serotonin synthesis in the neurons spared by the partial lesion or the near-complete neurotoxic lesion induced an increase in the number of striatal NPY neurons. These results suggest that complex adaptive mechanisms are probably responsible for the changes in striatal NPY reactivity observed after a partial lesion and that these neurons can adapt according to the extent of 5-HT depletion. Upon comparing the NPY responses in the dorsal and ventral components of the striatal complex, no main differences were observed; while in the caudate-putamen, the changes were primarily found to occur in the medial zone. This finding is discussed here with reference to the topographical effects of dopaminergic or glutamatergic deafferentation. Finally, these results suggest that a complete interruption of the 5-HT transmission may lead to an increase in the intracellular NPY level, which may be associated with a decrease in the release of the peptide. It can therefore be postulated that serotonergic neurons normally exert a positive influence on NPY striatal neurons.