Alcohol potently inhibits the kainate receptor-dependent excitatory drive of hippocampal interneurons

M. Carta, O. J. Ariwodola, J. L. Weiner, C. F. Valenzuela
Proceedings of the National Academy of Sciences. 2003-05-05; 100(11): 6813-6818
DOI: 10.1073/pnas.1137276100

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1. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6813-8. Epub 2003 May 5.

Alcohol potently inhibits the kainate receptor-dependent excitatory drive of
hippocampal interneurons.

Carta M(1), Ariwodola OJ, Weiner JL, Valenzuela CF.

Author information:
(1)Department of Neurosciences, University of New Mexico Health Sciences Center,
Albuquerque 87131, USA.

Kainate receptors (KA-Rs) are members of the glutamate-gated family of ionotropic
receptors, which also includes N-methyl-d-aspartate (NMDA) and
alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. KA-Rs are
important modulators of interneuron excitability in the CA1 region of the
hippocampus. Activation of these receptors enhances interneuron firing, which
robustly increases spontaneous inhibitory postsynaptic currents in pyramidal
neurons. We report here that ethanol (EtOH) potently inhibits this KA-R-mediated
effect at concentrations as low as those that can be achieved in blood after the
ingestion of just 1-2 drinks (5-10 mM). Pressure application of kainate, in the
presence of AMPA and NMDA receptor antagonists, evoked depolarizing responses in
interneurons that triggered repetitive action potential firing. EtOH potently
inhibited these responses to a degree that was sufficient to abolish action
potential firing. This effect appears to be specific for KA-Rs, as EtOH did not
affect action potential firing triggered by AMPA receptor-mediated depolarizing
responses. Importantly, EtOH inhibited interneuron action potential firing in
response to KA-R activation by synaptically released glutamate, suggesting that
our findings are physiologically relevant. KA-R-dependent modulation of glutamate
release onto pyramidal neurons was not affected by EtOH. Thus, EtOH increases
excitability of pyramidal neurons indirectly by inhibiting the KA-R-dependent
drive of gamma-aminobutyric acid (GABA)ergic interneurons. We postulate that this
effect may explain, in part, some of the paradoxical excitatory actions of this
widely abused substance. The excitatory actions of EtOH may be perceived as
positive by some individuals, which could contribute to the development of

DOI: 10.1073/pnas.1137276100
PMCID: PMC164529
PMID: 12732711 [Indexed for MEDLINE]

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