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 immu nocytochemical and In situ hybridization histochemical approaches. Top ographical analysis of the changes in Met-enkephalin (Met-enk) and sub stance P (SP) levels were performed on the rat striatum, globus pallid us 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) in to the anterior raphe nuclei. Both kinds of lesion led to significant increases (39-42%) in Met-enk immunoreactivity in the striatum; a corr esponding increase (21%) was detected in the globus pallidus only afte r severe 5-HT depletion. Only the severe lesion increased the SP immun oreactivity in the striatum (32%) and substantia nigra (26%). Neither striatal preproenkephalin nor preprotachykinin levels showed significa nt differences with the control values. These results suggest that the neuronal accumulation of Met-enk or SP may be attributable to post-tr anscriptional events, such as a blockade of the peptide release, and t hat 5-HT may, thus, exert a facilitatory influence on the striatal out put neurons. The results obtained after partial lesion indicate a pref erential sensitivity of striatal Met-enk vs. SP containing terminals t o the 5-HT denervation. These differences are illustrated in selective regional changes in peptide labeling. These data point to some balanc e exerted by the serotonergic and dopaminergic inputs on these neurona l populations. (C) 1997 Elsevier Science B.V.