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R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

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  • Bharanidharan Shanmugasundaram
  • Yogesh D Aher
  • Jana Aradska
  • Marija Ilic
  • Daniel Daba Feyissa
  • Predrag Kalaba
  • Nilima Y Aher
  • Vladimir Dragacevic
  • Babak Saber Marouf
  • Thierry Langer
  • Harald H Sitte
  • Harald Hoeger
  • Gert Lubec
  • Volker Korz

Abstract

Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.

Suggested Citation

  • Bharanidharan Shanmugasundaram & Yogesh D Aher & Jana Aradska & Marija Ilic & Daniel Daba Feyissa & Predrag Kalaba & Nilima Y Aher & Vladimir Dragacevic & Babak Saber Marouf & Thierry Langer & Harald , 2017. "R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity," PLOS ONE, Public Library of Science, vol. 12(6), pages 1-17, June.
    • Handle: RePEc:plo:pone00:0179675
    DOI: 10.1371/journal.pone.0179675
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    1. Uwe Frey & Richard G. M. Morris, 1997. "Synaptic tagging and long-term potentiation," Nature, Nature, vol. 385(6616), pages 533-536, February.
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