Inhibition by ethanol of excitatory amino acid receptors and nicotinic acetylcholine receptors at rat locus coeruleus neurons.
The frequency of spontaneous action potentials of locus coeruleus (LC) neurons was recorded extracellularly in pontine slices of the rat brain. Ethanol (1-100 mM) elevated the firing rate in most neurons; this effect was concentration-dependent. (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0.03-1 microM), kainate (0.1-3 microM), N-methyl-D-aspartate (NMDA; 1-30 microM), substance P (0.01-1 microM), nicotine (0.1-10 microM) and alpha,beta-methylene ATP (alpha,beta-meATP; 0.3-30 microM), all increased the firing. Application of ethanol (10-100 mM) to the superfusion medium for 10 min, reproducibly and concentration-dependently inhibited the facilitatory effect of NMDA (10 microM). However, the inhibitory effect of ethanol (100 mM) decreased during a 30-min superfusion period and after the wash-out of ethanol the sensitivity of LC neurons to NMDA (10 microM) tended to overshoot above their initial level. Although NMDA was more potent in the absence than in the presence of external Mg2+, ethanol (100 mM) continued to depress the facilitatory effect of a low concentration of NMDA (3 microM) in a Mg(2+)-free medium. By contrast, in a medium containing normal Mg2+, ethanol (100 mM) failed to significantly interfere with the increase in firing rate induced by a high concentration of NMDA (30 microM). The effects of kainate (0.5 microM), AMPA (0.3 microM) and nicotine (1 microM) were also depressed by ethanol (100 mM), while the effects of substance P (0.03 microM) and alpha,beta-meATP (30 microM) were not changed.(ABSTRACT TRUNCATED AT 250 WORDS)
Fröhlich
R
R
Pharmakologisches Institut der Universität, Freiburg, Germany.
Patzelt
C
C
Illes
P
P
D000200:Action Potentials; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008125:Locus Coeruleus / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017459:Receptors, Amino Acid / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology
D017459:Receptors, Amino Acid; D011978:Receptors, Nicotinic; D013373:Substance P; D000431:Ethanol; D016202:N-Methylaspartate; D009538:Nicotine; D007608:Kainic Acid