Selective effects of partial and severe lesions of the serotonergic systems on Met-enkephalin and substance P neurons in rat basal ganglia

The effects of partial (80%) vs. severe (>95%) depletion of serotonin (5-HT) on peptide expression in basal ganglia were examined using immunocytochemical and In situ hybridization histochemical approaches. Topographical analysis of the changes in Met-enkephalin (Met-enk) and substance P (SP) levels were performed on the rat striatum, globus pallidus and substantia nigra 3 weeks after injecting 3 mu l (partial lesion) or 6 mu l (severe lesion) 5,7-dihydroxytryptamine (6.6 mu g/mu l) into the anterior raphe nuclei. Both kinds of lesion led to significant increases (39-42%) in Met-enk immunoreactivity in the striatum; a corresponding increase (21%) was detected in the globus pallidus only after severe 5-HT depletion. Only the severe lesion increased the SP immunoreactivity in the striatum (32%) and substantia nigra (26%). Neither striatal preproenkephalin nor preprotachykinin levels showed significant differences with the control values. These results suggest that the neuronal accumulation of Met-enk or SP may be attributable to post-transcriptional events, such as a blockade of the peptide release, and that 5-HT may, thus, exert a facilitatory influence on the striatal output neurons. The results obtained after partial lesion indicate a preferential sensitivity of striatal Met-enk vs. SP containing terminals to the 5-HT denervation. These differences are illustrated in selective regional changes in peptide labeling. These data point to some balance exerted by the serotonergic and dopaminergic inputs on these neuronal populations. (C) 1997 Elsevier Science B.V.