title: Immature hippocampal neuronal networks do not develop tolerance to the excitatory actions of ethanol.
abstract: Ethanol (EtOH) damages the hippocampus, a brain region that is involved in learning and memory processes. The mechanisms responsible for this effect of EtOH are not fully understood. We recently demonstrated that acute EtOH exposure potently stimulates oscillatory activity driven by the excitatory actions of GABA in the CA3 region of the neonatal rat hippocampus. This activity can be recorded during the growth spurt period as giant depolarizing potentials (GDPs). Here, we characterized the effects of prolonged EtOH exposure on GDPs. In the first study, we prepared hippocampal coronal slices from neonatal rats and exposed these to control artificial cerebrospinal fluid (ACSF) or ACSF plus 50 mM EtOH for 3-4 h. We then performed whole-cell patch-clamp electrophysiological recordings from CA3 pyramidal neurons, which revealed that tolerance to the GDP stimulating effects of EtOH did not occur after continuous exposure. In the second study, we exposed neonatal rats to air or air plus 1.9 g/dl EtOH in vapor chambers for 4h/day for 1 or 3 days (neonatal peak blood EtOH concentration = 40-45 mM). We then performed slice electrophysiological studies 24 h after the end of EtOH exposure and found that there was no statistically significant difference in the acute effect of 50 mM EtOH on GDP frequency in samples from neonates exposed to air or air plus EtOH. These findings indicate that EtOH persistently stimulates network-driven oscillatory activity in the developing hippocampus. We propose that the lack of adaptive response to continuous EtOH exposure could make immature neuronal networks particularly vulnerable to the actions of this agent.
authors.affiliation: Department of Neurosciences, MSC08 4740, 1 University of New Mexico Health Sciences Center, Albuquerque, NM 87131-0001, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Galindo
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000494:pharmacology*; D004361:Drug Tolerance; D004594:Electrophysiology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects* / Q000254:growth & development*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D013268:Stimulation, Chemical
chemical_list: D002492:Central Nervous System Depressants; D011963:Receptors, GABA-A; D000431:Ethanol