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 intrani gral injections of colchicine in the rat forebrain using immunohistoch emistry and in situ hybridization. The observations on the injected si de 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 neurop eptide Y (NPY) in numerous nerve cell bodies of the limbic system (inj ected side), whereas the levels of the corresponding mRNAs are differe ntly modified according to the region examined. A clear correlation be tween 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 hypothal amic nucleus (SP). These observations are interpreted as an induction- or increased expression-of neuropeptide genes in neuronal perikarya po stsynaptic 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 effe ct). In the case where the enhancement of the immunoreactivity for the studied neuropeptides was associated with no change or a decreased ex pression of the corresponding genes in the same brain areas, colchicin e may have blocked the axoplasmic transport of peptides in nerve fiber s projecting to the midbrain and/or brain stem (6). This may result in a retrograde accumulation of peptides in the nerve cell bodies of ori gin and, eventually, in a negative feedback regulation of the correspo nding encoding genes in these perikarya (retrograde and presynaptic ef fect of colchicine). The drastic behavioral effects of bilateral intra nigral injections of colchicine, on ingestive behavior in particular, have been studied in a following paper.