NeuropharmacologyAcute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms
Section snippets
Hippocampal slice physiology
Hippocampal slices were prepared from P30–32 Sprague–Dawley rats using standard methods (Zorumski et al., 1996). Rats were anesthetized with halothane and decapitated. Hippocampi were rapidly dissected and placed in artificial cerebrospinal fluid (ACSF) containing (in mM): 124 NaCl, 5 KCl, 2 MgSO4, 2 CaCl2, 1.25 NaH2PO4, 22 NaHCO3, 10 glucose, bubbled with 95% O2–5% CO2 at 4–6°C, and cut transversely into 450μm slices using a vibrotome. Acutely prepared slices were placed in an incubation
Acute effects of ethanol on synaptic NMDARs
In initial experiments, we examined the effects of acute ethanol treatment on synaptic NMDARs in the CA1 region using low frequency activation of the Schaffer collateral pathway. When perfused for 10–15 min, ethanol inhibited synaptic NMDARs in a concentration-dependent fashion (Fig. 1A). At concentrations as high as 180mM, the block of NMDARs remained incomplete (67±10% inhibition, N=3). The effects of ethanol at concentrations up to 60mM were readily reversible following ethanol washout. At
Discussion
Ethanol is a non-competitive NMDAR antagonist that can inhibit the induction of NMDAR-dependent forms of LTP in the CA1 region of the hippocampus (see Allgaier 2002, Chandler 2003 for reviews). While NMDAR antagonism and LTP inhibition are thought to be related, there is evidence that ethanol’s actions on synaptic plasticity may be more complex than NMDAR inhibition (Schummers et al 1997, Schummers and Browning 2001). In our studies, we found that ethanol is a partial inhibitor of
Acknowledgments
This work was supported in part by NIH grants AA12951, AG 184334 and MH45493, and the Bantly Foundation.
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