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PMID: 1660156 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 23 ·1991-12-01 ·Pages 10936-40

Isaacson JS, Nicoll RA

Abstract

Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. These findings indicate that aniracetam slows the kinetics of fast synaptic transmission and are consistent with the proposal [Trussell, L. O. & Fischbach, G. D. (1989) Neuron 3, 209-218; Tang, C.-M., Dichter, M. & Morad, M. (1989) Science 243, 1474-1477] that receptor desensitization governs the strength of fast excitatory synaptic transmission in the brain.

MeSH Terms
Animals Evoked Potentials/drug effects Glutamates/pharmacology,physiology Guinea Pigs Hippocampus/drug effects,physiology In Vitro Techniques Kainic Acid/pharmacology Membrane Potentials/drug effects Pyramidal Tracts/drug effects,physiology Pyrrolidinones/pharmacology Quisqualic Acid/pharmacology Receptors, Glutamate Receptors, N-Methyl-D-Aspartate/drug effects,physiology Receptors, Neurotransmitter/drug effects,physiology Synapses/drug effects,physiology
Chemicals
Glutamates Pyrrolidinones Receptors, Glutamate Receptors, N-Methyl-D-Aspartate Receptors, Neurotransmitter aniracetam Quisqualic Acid Kainic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Isaacson J S
Physiology Graduate Program, University of California, San Francisco 94143-0450.
Nicoll R A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.23.10936
Published
1991-12-01
Pages
10936-40
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC53047
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.88.23.10936 PMC Full Text View journal details
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