DIFFERENTIAL-EFFECTS OF INTRACEREBROVENTRICULAR COLCHICINE ADMINISTRATION ON THE EXPRESSION OF MESSENGER-RNAS FOR NEUROPEPTIDES AND NEUROTRANSMITTER ENZYMES, WITH SPECIAL EMPHASIS ON GALANIN - AN INSITU HYBRIDIZATION STUDY

The axonal transport blocker clochicine has been extensively used in immunohistochemical studies to induce accumulation of neuroactive compounds, especially neuropeptides, in neuronal somata and thus improve their visualization. To assess whether colchicine might, in addition, ifluence the synthesis of such compounds, we have now used in situ hybridization to examine the level of mRNAs encoding for several neuropeptides (galanin[GAL], cholecystokinn [CCK], somatostatin [sOM], neuropeptide Y[NPY]) and neurotransmitter‐synthesizing enzymes (chloine acetyltransferase [ChAT], tyrosine hydroxylase [TH], amino acid decarboxylase [AADC], and glutamic acid decarboxylase [GAD]) after intraventricular administration of the drug. The results show that colchicine differntially modifies the level of several mRNA species in different brain areas. Thus GAL mRNA levels increase in virtually all regions examined, including the basal forebrain, hypothalamus, dorsal raphe nucleus, locus coeruleus to be induced in the ipsilateral hemisphere in region such as the cortex, hippocampus, striatum, lateral septum, and some nuclei of the thalamus as well as within white matter, where it cannot be detected in control animals. Although GAL mRAN in the vast majority of cases is neuronal, some findigs indicate a possible glial localization. In parallel, clochicine depletes chAT mRNA and increase GAD mRNA in the basal forbrain and striatum and decreases AADC mRNA in the dorsal raphe nucleus and locus coeruleus. In the latter nucleus, NPY and TH mRNA level are increased by clochcine. In contrast, TH mRNA and also CCK mRNA level decrease in the substantia nigra. In the cortex, hippocampus, and thalamus ipsilateral to colchicine injection CCK mRNA level are markedly decrease, whereas sOM mRNA level decreas and NPY mRNA increase in the hippocampus, but unchanged in the cortex. The result are discussed with reference to the possible artifacts that the use of colchicine might induce in immunohistochemical mapping studies and in relation to possible neurotoxic action of colchicine, in some cases perhaps related to impaired retrograde transport of growth factor(s). Copyright © 1990 Wiley‐Liss, Inc.