CHRONIC NICOTINE TREATMENT COUNTERACTS NIGRAL CELL LOSS INDUCED BY A PARTIAL MESODIENCEPHALIC HEMITRANSECTION - AN ANALYSIS OF THE TOTAL NUMBER AND MEAN VOLUME OF NEURONS AND GLIA IN SUBSTANTIA-NIGRA OF THE MALE-RAT

This study combines immunocytochemical and stereological methods for t he first time to obtain unbiased estimates of the number of cells in t he entire substantia nigra and their respective mean volume. Nicotine, delivered by subcutaneously implanted osmotic pumps (0.125 mg/kg/h, 1 4 days) to male Sprague-Dawley rats with a partial unilateral mesodien cephalic lesion, caused a significant counteraction of the lesion-indu ced reduction in total number of nigral tyrosine hydroxylase-like immu noreactive neurons counterstained with Cresyl Violet compared with sal ine treated control animals. The number of Nissl stained neurons witho ut tyrosine hydroxylase-like immunoreactivity was not affected by the lesion nor by nicotine. The numbers of non-neuronal glial fibrillary a cidic protein-like immunoreactive cells counterstained with Cresyl Vio let and smaller cells seen after Cresyl Violet staining alone, possibl y representing microglia, were increased by the lesion but not affecte d by nicotine. No nicotine-induced effects were found on the number of nigral cells located contralateral to the lesion. The lesion-induced reduction in the mean volume of the nigral cells showing tyrosine hydr oxylase-like immunoreactivity, as determined with the stereological ro tator method, was not affected by nicotine. These findings suggest tha t continuous nicotine infusion exerts protective effects on lesioned n igroneostriatal dopamine systems and that these protective effects are selective for the nigral dopamine neurons not affecting other populat ions of neurons or non-neuronal cells. This neuroprotective effect mig ht lead to new therapeutic strategies in clinical neurodegenerative di sorders such as Parkinson's Disease.