EFFECTS OF INTRANIGRAL INJECTIONS OF COLCHICINE ON THE EXPRESSION OF SOME NEUROPEPTIDES IN THE RAT FOREBRAIN - AN IMMUNOHISTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDY

In the present study, we describe the neurochemical effects of intranigral injections of colchicine in the rat forebrain using immunohistochemistry and in situ hybridization. The observations on the injected side are compared to the contralateral one and to the sham-operated rats. We demonstrate that such injections are able to strongly enhance the immunoreactivity for Met-enkephalin (ME), substance P (SP) and neuropeptide Y (NPY) in numerous nerve cell bodies of the limbic system (injected side), whereas the levels of the corresponding mRNAs are differently modified according to the region examined. A clear correlation between the enhancement of the immunostaining for ME and SP and that of the preproenkephalin (PPA) and preprotachychinin gene transcripts was observed in neuronal perikarya of the medial amygdaloid nucleus (SP), of the dorsolateral hypothalamus (ME) and of the ventromedial hypothalamic nucleus (SP). These observations are interpreted as an induction-or increased expression-of neuropeptide genes in neuronal perikarya postsynaptic to nerve fibers originating in the midbrain and brain stem. In this case, colchicine is thought to block the electrophysiological activity of ascending nerve fibers (anterograde and postsynaptic effect). In the case where the enhancement of the immunoreactivity for the studied neuropeptides was associated with no change or a decreased expression of the corresponding genes in the same brain areas, colchicine may have blocked the axoplasmic transport of peptides in nerve fibers projecting to the midbrain and/or brain stem (6). This may result in a retrograde accumulation of peptides in the nerve cell bodies of origin and, eventually, in a negative feedback regulation of the corresponding encoding genes in these perikarya (retrograde and presynaptic effect of colchicine). The drastic behavioral effects of bilateral intranigral injections of colchicine, on ingestive behavior in particular, have been studied in a following paper.