CHRONIC CONTINUOUS-INFUSION OF NICOTINE INCREASES THE DISAPPEARANCE OF CHOLINE-ACETYLTRANSFERASE IMMUNOREACTIVITY IN THE CHOLINERGIC CELL-BODIES OF THE MEDIAL SEPTAL NUCLEUS FOLLOWING A PARTIAL UNILATERAL TRANSECTION OF THE FIMBRIA-FORNIX

Previous studies have demonstrated that chronic continuous nicotine tr eatment via minipumps partially protects against mechanically induced degeneration of the nigrostriatal dopamine neurons in the male Sprague -Dawley rat. In the present study we investigated how a 4-week continu ous infusion with (-)-nicotine via minipumps implanted subcutaneously in the male Sprague-Dawley rat (0.125 mg/kg-1 h-1) influences the ante rograde and retrograde changes occurring in the septohippocampal choli nergic neurons following a unilateral transection of the fimbria forni x. Choline acetyltransferase and acetylcholinesterase immunocytochemis try was performed in combination with computer-assisted morphometry an d microdensitometry. Measurements of choline acetyltransferase enzyme activity was performed in the dorsal hippocampus. The chronic nicotine infusion significantly increased the disappearance of the choline ace tyltransferase immunoreactive nerve cell area within the medial septal nucleus of the lesioned side. However, the disappearance of the acety lcholinesterase immunoreactive nerve terminals within the dentate gyru s (molecular layer) and of choline acetyltransferase enzyme activity w ithin the dorsal hippocampus was not found to be influenced by the chr onic nicotine infusion. Thus, chronic infusion of (-)-nicotine does no t appear to exert any protective activity on mechanically injured sept ohippocampal cholinergic neurons but may instead increase their dysfun ction. In comparison with the dopaminergic neurons it may therefore be that the continuous chronic nicotine exposure does not lead to suffic ient desensitization of the nicotinic cholinoceptors of the cholinergi c neurons to reduce the chronic influx of sodium and calcium ions via the nicotinic ion channels and thus intraneuronal calcium levels and e nergy demands. Interactions between the high-affinity tyrosine kinase receptors for the neurotrophins and other growth factors and the nicot inic receptors may also be different from those taking place within th e nigral dopaminergic neurons. Thus, heterogeneities may exist among c entral neuronal systems with regard to their trophic responses to chro nic continuous nicotine treatment.