TY - JOUR
T1 - Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus
AU - Kornum, Birgitte R
AU - Weikop, Pia
AU - Moller, Arne
AU - Ronn, Lars C B
AU - Knudsen, Gitte M
AU - Aznar, Susana
PY - 2006/2/16
Y1 - 2006/2/16
N2 - 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.
AB - 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.
KW - Acetylcholine/metabolism
KW - Animals
KW - Cell Count/methods
KW - Chromatography, High Pressure Liquid/methods
KW - Drug Interactions
KW - Fenclonine/pharmacology
KW - Fenfluramine/pharmacology
KW - Gene Expression/drug effects
KW - Hippocampus/cytology
KW - Hydroxyindoleacetic Acid/metabolism
KW - Immunohistochemistry/methods
KW - Male
KW - Neurons/drug effects
KW - Neuroprotective Agents/pharmacology
KW - Phenylcarbamates/pharmacology
KW - Proto-Oncogene Proteins c-fos/metabolism
KW - Rats
KW - Rats, Sprague-Dawley
KW - Rivastigmine
KW - Serotonin/deficiency
KW - Serotonin Uptake Inhibitors/pharmacology
U2 - 10.1016/j.brainres.2005.12.030
DO - 10.1016/j.brainres.2005.12.030
M3 - Journal article
C2 - 16426583
SN - 0006-8993
VL - 1073-1074
SP - 262
EP - 268
JO - Brain Research
JF - Brain Research
ER -