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Alcohol and Alcoholism Vol. 38, No. 5, pp. 394-399, 2003
© 2003 Medical Council on Alcohol

EFFECTS OF ACUTE ETHANOL ON THE Ca2+ RESPONSE TO AMPA IN CULTURED RAT CORTICAL GABAergic NONPYRAMIDAL NEURONS

Wolfgang Fischer*, Heike Franke and Peter Illes

Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Germany

(Received 21 June 2002; first review notified 3 September 2002; in revised form 28 March 2003; accepted 20 May 2003)

Aims and Methods: Immunocytochemical studies revealed that the vast majority of neurons in our primary cultures of rat cortical cells are GABA-positive and represent nonpyramidal interneuron-like cells. The influence of ethanol on (S)-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced Ca2+ influx was investigated in multipolar, medium-sized neurons by using single-cell fura-2 microfluorimetry. Results: In a first series of experiments, the results showed a small but significant decrease of 17–22% by ethanol (100 mm) of the intracellular Ca2+ signals induced by slowly superfused AMPA (10, 30, 100 µm). This finding is comparable with the inhibitory activity of ethanol on N-methyl-D-aspartic acid (NMDA)-induced Ca2+ signals in these cells. Further studies with a fast pressure-application of AMPA (30 µm) showed a similar degree of inhibition by ethanol (100 mm). Superfusion with tetrodotoxin/bicuculline, to rule out possible effects of spontaneously released GABA and synaptic spike activity, did not significantly influence the AMPA-induced Ca2+ response nor the inhibitory effect of ethanol. Conclusions: The present findings indicate that ethanol at high concentrations inhibits Ca2+ signaling via both AMPA and NMDA glutamate receptors in cortical interneuron-like cells. These effects may contribute to the central depressant action of this drug.


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