Ethanol inhibits the N-methyl-D-aspartate (NMDA)-induced attenuation of the NMDA-evoked noradrenaline release in the rat brain cortex: interaction with NMDA-induced desensitization

Abstract

The influence of ethanol, AP5 (DL-2-amino-5-phosphonopentanoic acid) and dizocilpine (MK-801) ((+)-5-methyl-10,11-dihydro-5H-dibenzo (a,b)-cyclo-hept-5,10-imine hydrogen maleate) on the NMDA-induced attenuation of the NMDA-evoked noradrenaline release was examined in rat brain cortex slices preincubated with 3H-noradrenaline. The slices were superfused with Mg(2+)-free Krebs-Henseleit solution. Tritium overflow (corresponding to 3H-noradrenaline release) was stimulated by 300 mumol/l NMDA for 2 min. Presence of 10-100 mumol/l NMDA from 20 to 2 min before stimulation concentration-dependently inhibited the NMDA (300 mumol/l)-evoked 3H overflow, suggesting an agonist-induced desensitization attributable to the modification of events at the NMDA receptor itself and/or distal to this receptor system. The desensitizing effect of 100 mumol/l NMDA was almost complete and was not diminished when the time of preexposure was decreased to 10 min, and when NMDA was removed from the superfusion fluid for up to 5 min before the stimulus; however, the desensitizing effect was reduced after further decrease in the duration of preexposure to NMDA or further prolongation of the interval between preexposure and stimulation. Ethanol inhibited the NMDA-induced 3H overflow (IC50 45 mmol/l); this effect was almost abolished when ethanol was omitted from the superfusion fluid from 2 min before stimulation onward. Ethanol, when simultaneously present with 100 mumol/l NMDA in the superfusion fluid from 20 to 2 min before the NMDA stimulus, concentration-dependently (IC50 112 mmol/l) decreased the inhibitory effect of NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)