Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus
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Interactions between the serotonergic and cholinergic systems are known to occur and are believed to play a role in the mechanism underlying both major depression and Alzheimer's disease. On a molecular level, studies suggest that acetylcholine (ACh) increases serotonin (5-HT) release through nicotinic receptors located at nerve terminals. The aim of the present study was to determine in which areas and to what extent 5-HT mediates the neuronal response to ACh release. For this purpose, neuronal activity was measured in rats with rivastigmine-induced elevated ACh levels after a 95% 5-HT depletion obtained by dosing p-chlorophenylalanine followed by D,L-fenfluramine. Neuronal activation was quantified by stereological measurements of c-Fos immunoreactivity. The brain areas examined were medial prefrontal cortex, septum, dorsal hippocampus, and dorsal raphe nucleus. Rivastigmine significantly increased c-Fos immunoreactivity in medial prefrontal cortex and the hippocampus, but not in the septum and dorsal raphe nucleus. 5-HT depletion decreased ACh-induced c-Fos immunoreactivity in the dentate gyrus. By contrast, 5-HT depletion had no effect on the ACh-induced activity in the other brain areas examined. It is concluded that 5-HT mediates part of the ACh-induced hippocampal neuronal activation, possibly mediated via locally released 5-HT.
|Journal||Brain Research Reviews|
|Number of pages||7|
|Publication status||Published - 16 Feb 2006|
- Acetylcholine/metabolism, Animals, Cell Count/methods, Chromatography, High Pressure Liquid/methods, Drug Interactions, Fenclonine/pharmacology, Fenfluramine/pharmacology, Gene Expression/drug effects, Hippocampus/cytology, Hydroxyindoleacetic Acid/metabolism, Immunohistochemistry/methods, Male, Neurons/drug effects, Neuroprotective Agents/pharmacology, Phenylcarbamates/pharmacology, Proto-Oncogene Proteins c-fos/metabolism, Rats, Rats, Sprague-Dawley, Rivastigmine, Serotonin/deficiency, Serotonin Uptake Inhibitors/pharmacology