Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus.
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.
Kornum
Birgitte R
BR
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. birgitte@nru.dk
Weikop
Pia
P
Moller
Arne
A
Ronn
Lars C B
LC
Knudsen
Gitte M
GM
Aznar
Susana
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002452:Cell Count / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D048448:Phenylcarbamates / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068836:Rivastigmine; D012701:Serotonin / Q000172:deficiency*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D000109:Acetylcholine; D010134:Fenclonine; D005277:Fenfluramine; D006897:Hydroxyindoleacetic Acid; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D016760:Proto-Oncogene Proteins c-fos; D000068836:Rivastigmine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors