Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We have investigated the mechanisms by which acute ethanol inhibits the induction of long-term potentiation (LTP) in area CA1 of the rat hippocampal slice. In a previous report [Alcohol. Clin. Exp. Res. 21 (1997) 404] we demonstrated that ethanol produces only a modest inhibition of pharmacologically isolated N-methyl-D-aspartate receptors (NMDAR) in the CA1 region of the hippocampus. Moreover, this level of inhibition was not sufficient to account for ethanol's complete inhibition of LTP induction in this brain region. One possible explanation of these results is that we may have underestimated ethanol's ultimate effect on the NMDAR by focusing on pharmacologically isolated NMDAR responses. Ethanol might indirectly inhibit the NMDAR by, for example, potentiating the GABA(A)R. To explore this possibility, we first examined the effects of the GABA(A)R antagonist picrotoxin (PTX) and the allosteric GABA(A)R modulator flunitrazepam on NMDAR responses. We demonstrate that these modulators of GABA(A)R activity significantly affect the magnitude of synaptically evoked NMDAR responses. We next examined the effects of ethanol on NMDAR responses in the presence and absence of PTX. We see a significantly greater ethanol inhibition of the NMDAR when GABA(A)Rs are functional, i.e. in the absence of PTX. These data suggest that ethanol produces an inhibition of the NMDAR indirectly by affecting the GABA(A)R neurotransmission. Moreover, we found that ethanol inhibition of NMDAR activity, both directly through actions on the NMDAR, and indirectly, possibly through potentiation of GABA(A)R activity, is sufficient to account for ethanol's complete blockade of LTP induction.


Journal article


Brain Res Mol Brain Res

Publication Date





9 - 14


Animals, Central Nervous System Depressants, Ethanol, Excitatory Amino Acid Antagonists, Excitatory Postsynaptic Potentials, GABA Antagonists, Long-Term Potentiation, Male, Memory, Organ Culture Techniques, Organophosphorus Compounds, Picrotoxin, Quinoxalines, Rats, Rats, Sprague-Dawley, Receptors, GABA-A, Receptors, N-Methyl-D-Aspartate, Synaptic Transmission