Nefiracetam and galantamine modulation of excitatory and inhibitory synaptic transmission via stimulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons

S. Moriguchi, X. Zhao, W. Marszalec, J. Z. Yeh, K. Fukunaga, T. Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The cholinergic and glutamatergic systems are known to be downregulated in the brain of Alzheimer's disease patients. Galantamine and nefiracetam have been shown to potentiate the phasic activity of nicotinic acetylcholine receptors (nAChRs) in the brain. Stimulation of nAChRs is also known to cause release of various neurotransmitters including glutamate and γ-aminobutyric acid (GABA). We have previously reported that nefiracetam and galantamine potentiate the activity of nAChRs. Therefore, nefiracetam and galantamine are hypothesized to cause stimulations of the glutamate and GABA systems via stimulation of nAChRs. The present study was set out to test this hypothesis by measuring the effects of these drugs on spontaneous miniature excitatory postsynaptic currents (mEPSCs) and spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded by the whole-cell patch clamp technique from rat cortical neurons in primary cultures. Acetylcholine (ACh) at 30 nM generated a steady inward current and increased the frequency of mEPSCs and mIPSCs. Nefiracetam at 10 nM plus 30 nM ACh increased the frequency of mEPSCs and mIPSCs beyond the levels increased by ACh alone. The potentiating action of nefiracetam was abolished by dihydro-β-erythroidine. None of these treatments affected the amplitude of mEPSCs or mIPSCs. Galantamine at 1 μM plus ACh did not significantly potentiate the frequency. Nefiracetam at 10 nM had no effect on neurons that did not respond to 30 nM ACh. It was concluded that the nefiracetam released glutamate via stimulation of the α4β2 nAChRs.

Original languageEnglish (US)
Pages (from-to)484-491
Number of pages8
JournalNeuroscience
Volume160
Issue number2
DOIs
StatePublished - May 5 2009

Keywords

  • Alzheimer's drug
  • GABAergic system
  • cholinergic system
  • excitatory postsynaptic current
  • glutamatergic system
  • inhibitory postsynaptic current

ASJC Scopus subject areas

  • Neuroscience(all)

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