Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus

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 -