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)--amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0.03–1 M), kainate ( 0.1–3 M), N-methyl-D-aspartate (NMDA; 1–30 M), substance P 0.01–1 M, nicotine 0.1–10 M and ,-methylene ATP ,-meATP; 0.3–30 M, all increased the firing. Application of ethanol g10–100 mM to the superfusion medium for 10 min, reproducibly and concentration-dependently inhibited the facilitatory effect of NMDA g10 M. However, the inhibitory effect of ethanol (100 mM) decreased during a 30-min superfusion period and after the washout of ethanol the sensitivity of LC neurons to NMDA (10 M) 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 (EM) in a Mg²⁺-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 M). The effects of kainate (0.5 M), AMPA (0.3 M) and nicotine (1 M) were also depressed by ethanol (100 M), while the effects of substance P (0.03 M) and ,-meATP (30 M) were not changed. In conclusion, ethanol selectively counteracts the opening of cationic channels caused by excitatory amino acid (EAA) receptor agonists and nicotinic acetylcholine receptor agonists. During a longer lasting incubation with ethanol, the inhibition of the NMDA-induced excitatory effect declines, indicating the development of tolerance.Correspondence to: P. Illes at the above address