N-methyl-D-aspartate-stimulated increases in intracellular calcium exhibit brain regional differences in sensitivity to inhibition by ethanol.
This study compared N-methyl-D-aspartate (NMDA)-stimulated increases in intracellular calcium in fura-2-loaded neurons dissociated from newborn rat brainstem (EC50 in microM; 6.4), cerebellum (9.5), forebrain (6.3), and hippocampus (10.6). Ethanol inhibition of the response to 25 microM NMDA differed among the regions. The NMDA response in hippocampus was inhibited by 20 mM ethanol; cortex and cerebellum responses were inhibited by 80 mM ethanol, and no inhibition was seen in the brainstem. Addition of glycine (15 microM) failed to attenuate ethanol inhibition of the NMDA response. These results demonstrate that ethanol inhibition of NMDA-stimulated responses varies according to brain region. In contrast to previous findings from this laboratory using dissociated neurons from whole brain, the addition of glycine did not reverse the inhibitory effects of ethanol on NMDA-stimulated responses.
Randoll
L A
LA
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712-1074, USA.
Wilson
W R
WR
Weaver
M S
MS
Spuhler-Phillips
K
K
Leslie
S W
SW
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D000431:Ethanol; D016202:N-Methylaspartate; D002118:Calcium; D005998:Glycine