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 bra in. Ethanol (1-100 mM) elevated the firing rate in most neurons; this effect was concentration-dependent. lpha-amino-3-hydroxy-5-methyl-4-is oxazolepropionic acid (AMPA; 0.03 -1 mu M), kainate (0.1-3 mu M), N-me thyl-D-aspartate (NMDA; 1-30 mu M), substance P (0.01-1 mu M), nicotin e (0.1-10 mu M) and alpha,beta-methylene ATP (alpha,beta-meATP; 0.3-30 mu M), all increased the firing. Application of ethanol (10-100 mM) t o the superfusion medium for 10 min, reproducibly and concentration-de pendently inhibited the facilitatory effect of NMDA (10 mu 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 mu M) tended to overshoot above their initial level. Although NMDA was more potent in the absence than in the presen ce of external Mg2+, ethanol (100 mM) continued to depress the facilit atory effect of a low concentration of NMDA (3 mu M) in a Mg2+-free me dium. By contrast, in a medium containing normal Mg2+, ethanol (100 mM ) failed to significantly interfere with the increase in firing rate i nduced by a high concentration of NMDA (30 mu M). The effects of kaina te (0.5 mu M), AMPA (0.3 mu M) and nicotine (1 mu M) were also depress ed by ethanol (100 mM), while the effects of substance P (0.03 mu M) a nd alpha,beta-meATP (30 mu M) were not changed. In conclusion, ethanol selectively counteracts the opening of cationic channels caused by ex citatory amino acid (EAA) receptor agonists and nicotinic acetylcholin e receptor agonists. During a longer lasting incubation with ethanol, the inhibition of the NMDA-induced excitatory effect declines, indicat ing the development of tolerance.