Evidence for the ability of hippocampal neurons to develop acute toleranceto ethanol in behaving rats

Background: The cellular mechanisms underlying acute tolerance to alcohol a re unclear. This study aimed to determine whether hippocampal neurons have the ability to develop acute tolerance to alcohol in behaving rats. Methods : Intrahippocampal microdialysis was performed in freely behaving rats, and the tiring of single neurons in the dialysis area was recorded. The contro l microdialysis fluid, artificial cerebrospinal fluid (ACSF), was replaced with 1 M ethanol in ACSF for a 30 min period. One hour later, the ethanol p erfusion was repeated. To test the functional integrity of the microdialysi s probe in situ, each microdialysis session was completed with recording th e effect of a 10-20 min perfusion of 500 muM N-methyl-D-aspartate (NMDA). T he extracellular concentration profile of ethanol during intrahippocampal m icrodialysis with 1 M ethanol was estimated in a separate study in anesthet ized rats. The ethanol content was measured in tissue slices surrounding th e probe with gas chromatography (GC), and the generated data were analyzed with a mathematical model for microdialysis to estimate the concentration o f ethanol at the recording site. Results: The predominant effect of the fir st intrahippocampal microdialysis with ethanol was a decrease in firing rat e in both pyramidal cells and interneurons. In contrast, such tiring rate d ecrease did not develop during the second ethanol perfusion. Subsequent NMD A perfusion still induced robust changes in the electrical activity of the neurons. The estimated extracellular ethanol concentration at the recording site was 45-70 mM. Conclusion: This study revealed that hippocampal neuron s have the ability to develop acute tolerance to a single exposure of clini cally relevant concentrations of ethanol in behaving rats, without influenc es from the rest of the body. (C) 2001 Elsevier Science B.V. All rights res erved.