Inhibition by ethanol of excitatory amino acid receptors in rat locus coeruleus neurons in vitro.
Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). In a first series of experiments, various parameters of spontaneous action potentials were evaluated. It turned out that ethanol (100 mM) does not alter the firing rate, the spike amplitude and the afterhyperpolarization following a spike. In subsequent experiments, the generation of action potentials was prevented by passing continuous hyperpolarizing current via the recording electrode. Under these conditions, ethanol (100 mM) had no effect on the membrane potential or input resistance. Pressure-applied N-methyl-D-aspartate (NMDA), (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and alpha,beta-methylene ATP (alpha,beta-meATP) reproducibly depolarized LC neurons. While ethanol (100 mM) depressed the NMDA- and AMPA-induced depolarization to a similar extent, it did not interact with alpha,beta-meATP. Lower concentrations of ethanol (10 and 30 mM) had no effect on depolarizing responses to NMDA or AMPA. Noradrenaline applied by pressure pulses reproducibly hyperpolarized LC cells. These hyperpolarizations were unchanged by ethanol (100 mM). Biphasic synaptic potentials consisting of early depolarizing (PSP) and late hyperpolarizing (IPSP) components were evoked by electrical stimulation. Ethanol (100 mM) depressed the PSP and increased the IPSP. Glutamatergic PSPs recorded in the combined presence of picrotoxin (100 microM) and suramin (100 microM) were also inhibited by ethanol (100 mM). However, IPSPs recorded under these conditions were insensitive to ethanol (100 mM). In conclusion, ethanol may interfere with the AMPA (or NMDA) receptor-mediated fraction of the PSP and slightly facilitate the alpha2 adrenoceptor-mediated fraction of the IPSP.
Nieber
K
K
Institut für Pharmazie der Universität, Pharmakologie für Naturwissenschaftler, Leipzig, Germany.
Poelchen
W
W
Sieler
D
D
Illes
P
P
D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D058910:Purinergic P2 Receptor Agonists; D017470:Receptors, Glutamate; D000431:Ethanol