Differential effect of ethanol on NMDA EPSCs in pyramidal cells in the posterior cingulate cortex of juvenile and adult rats.
Ethanol (EtOH) is a potent inhibitor of N-methyl-D-aspartate (NMDA) receptor-mediated activity in a number of brain areas, and recent studies have indicated that this inhibitory effect of ethanol is more powerful in the juvenile brain compared with the adult brain. However, previous direct developmental comparisons have been limited to studies of extracellular responses in the hippocampus. To begin an assessment of the mechanisms underlying this developmental sensitivity, we assessed the inhibitory effect of EtOH on NMDA receptor-mediated synaptic transmission in neocortical slices from adult (95-135 days old) and juvenile (28-32 days old) rats using the whole cell patch-clamp recording technique. In the presence of 6,7-dinitroquinoxaline-2,3-dione (20 microM) and bicuculline methiodine (20 microM), NMDA receptor-mediated excitatory postsynaptic currents were isolated from pyramidal cells of the posterior cingulate cortex (PCC). In slices from juvenile rats 5, 10, 30, and 60 mM EtOH reduced the mean amplitude of NMDA receptor-mediated EPSCs by 11, 22, 35, and 46%, respectively. However, the same concentrations of EtOH inhibited the mean amplitude of EPSCs by only 4, 8, 15, and 31% in slices from adult rats. This developmental difference in the potency of EtOH against NMDA receptor-mediated EPSCs was also observed when the holding potential of the neurons was increased to +30 mV, although the inhibitory effect of ethanol on adult neurons was diminished at that voltage. These results provide a cellular analysis of the enhanced potency of ethanol against NMDA receptor-mediated EPSCs in neocortical cells from juvenile animals compared with adults.
Li
Qiang
Q
Department of Pharmacology and Cancer Biology, Neurology Research, Veterans Affairs Medical Center, 508 Fulton Street, Durham, North Carolina 27705, USA. Liq@duke.edu
Wilson
Wilkie A
WA
Swartzwelder
H Scott
HS
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006179:Gyrus Cinguli / Q000166:cytology*; D008297:Male; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; C017069:bicuculline methiodide; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline