Prucalopride and donepezil act synergistically to reverse scopolamine-induced memory deficit in C57Bl/6j mice. Cachard-Chastel, M., Devers, S., Sicsic, S., Langlois, M., Lezoualc'h, F., Gardier, A. M., & Belzung, C. Behavioural Brain Research, 187(2):455--461, March, 2008.
doi  abstract   bibtex   
It is known that 5-HT(4) receptor agonists increase sAPPalpha levels in the cortex and hippocampus of mice as well as in a model of Alzheimer's disease (AD). As sAPPalpha is thought to have pro-mnesic properties, we assessed whether its increase induces cognitive improvement in a spatial memory task and whether it reverses a scopolamine-induced memory deficit. Mice treated or not treated with scopolamine were trained in the Morris water maze for 3 days. Before the probe test, they received an injection of either a 5-HT(4) receptor agonist (prucalopride or RS 67333), or an acetylcholinesterase inhibitor (donepezil), or both drugs. As expected, scopolamine decreased performance, an effect that was not reversed by the drugs tested when injected alone. However, prucalopride (5 mg kg(-1), s.c.) acted synergistically with donepezil (0.75 mg kg(-1), s.c.) to counteract completely scopolamine-induced amnesia. Western blot analysis of tissue homogenates in the cortex and hippocampus shows that sAPPalpha levels did not differ between saline- and scopolamine-treated mice. Furthermore, a region-dependent drug action was observed since the scopolamine-treated mice display a tendency to increase sAPPalpha levels in the hippocampus after donepezil or in the cortex after prucalopride. Our results suggest that a combined treatment with a 5-HT(4) receptor agonist with an acetylcholinesterase inhibitor has beneficial effects on memory in mice. Moreover, it seems to enhance sAPPalpha levels in two brain regions highly affected in AD. Thus, a drug polytherapy could be interesting not only to enhance cognitive performance and decrease drawbacks but also to get the best action in each brain region.
@article{ cachard-chastel_prucalopride_2008,
  title = {Prucalopride and donepezil act synergistically to reverse scopolamine-induced memory deficit in C57Bl/6j mice},
  volume = {187},
  issn = {0166-4328},
  doi = {10.1016/j.bbr.2007.10.008},
  abstract = {It is known that 5-{HT}(4) receptor agonists increase {sAPPalpha} levels in the cortex and hippocampus of mice as well as in a model of Alzheimer's disease ({AD}). As {sAPPalpha} is thought to have pro-mnesic properties, we assessed whether its increase induces cognitive improvement in a spatial memory task and whether it reverses a scopolamine-induced memory deficit. Mice treated or not treated with scopolamine were trained in the Morris water maze for 3 days. Before the probe test, they received an injection of either a 5-{HT}(4) receptor agonist (prucalopride or {RS} 67333), or an acetylcholinesterase inhibitor (donepezil), or both drugs. As expected, scopolamine decreased performance, an effect that was not reversed by the drugs tested when injected alone. However, prucalopride (5 mg kg(-1), s.c.) acted synergistically with donepezil (0.75 mg kg(-1), s.c.) to counteract completely scopolamine-induced amnesia. Western blot analysis of tissue homogenates in the cortex and hippocampus shows that {sAPPalpha} levels did not differ between saline- and scopolamine-treated mice. Furthermore, a region-dependent drug action was observed since the scopolamine-treated mice display a tendency to increase {sAPPalpha} levels in the hippocampus after donepezil or in the cortex after prucalopride. Our results suggest that a combined treatment with a 5-{HT}(4) receptor agonist with an acetylcholinesterase inhibitor has beneficial effects on memory in mice. Moreover, it seems to enhance {sAPPalpha} levels in two brain regions highly affected in {AD}. Thus, a drug polytherapy could be interesting not only to enhance cognitive performance and decrease drawbacks but also to get the best action in each brain region.},
  language = {eng},
  number = {2},
  journal = {Behavioural Brain Research},
  author = {Cachard-Chastel, M. and Devers, S. and Sicsic, S. and Langlois, M. and Lezoualc'h, F. and Gardier, A. M. and Belzung, C.},
  month = {March},
  year = {2008},
  pmid = {18061284},
  keywords = {Amyloid beta-Protein Precursor, Analysis of Variance, Aniline Compounds, Animals, Benzofurans, Cerebral Cortex, Cholinesterase Inhibitors, Drug Synergism, Hippocampus, Indans, Male, Maze Learning, Memory Disorders, Mice, Mice, Inbred C57BL, Motor Activity, Nootropic Agents, Piperidines, Scopolamine Hydrobromide, Serotonin 5-{HT}4 Receptor Agonists, Statistics, Nonparametric},
  pages = {455--461}
}

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