Chronic ethanol exposure enhances [3H]GABA release and does not affect GABAA receptor mediated 36Cl uptake.
Chronic ethanol treatment (CET) produces a permanent reduction in hippocampal long-term potentiation (LTP). The CET produced reduction of LTP can be eliminated acutely by pharmacological blockade of gamma-aminobutyric acid (GABA)ergicA synaptic transmission with the specific antagonist, bicuculline methiodide. Since LTP induction is normally modulated by activation of GABAergic synaptic transmission, we hypothesized that CET reduced LTP by enhancing either postsynaptic GABAA channel function or GABA release from presynaptic terminals. In the present study, we examined the long term effects of CET on GABAA channel function by measuring the efficacy of GABA to stimulate and bicuculline to antagonize GABA-stimulated 36Cl- uptake in hippocampal and cortical membrane preparations. CET did not affect basal uptake of chloride or the efficacy of either GABA or bicuculline at the GABAA channel. We next measured the long term effects of CET on basal and stimulated GABA release. When basal and electrically-stimulated [3H]GABA release were measured in superfused hippocampal slices, stimulated release was increased by 30% in CET rats. Basal release was unaffected. Thus it appears that CET may be reducing LTP by enhancing plasticity-related GABA release from presynaptic terminals.
Department of Neuroscience, J. Hillis Miller Health Center, University of Florida, Gainesville 32610.
M F
MF
Tremwel
B E
BE
Hunter
J
J
Peris
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D002713:Chlorine; D000431:Ethanol / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D011868:Radioisotopes; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D011868:Radioisotopes; D011963:Receptors, GABA-A; D000431:Ethanol; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline