A calcium channel antagonist stereoselectively decreases ethanol withdrawal hyperexcitability but not that due to bicuculline, in hippocampal slices.
1. Extracellular recordings were made from CA1 area of isolated hippocampal slices of the mouse after chronic ethanol administration in vivo, with orthodromic stimulation of the Schaffer collateral/commissural fibres. 2. The (+)-isomer of the calcium channel antagonist PN 200-110 (isradipine) significantly decreased all the recorded signs of hyperexcitability in the slices during ethanol withdrawal. These included increased paired pulse potentiation and decreases in the thresholds for elicitation of single and multiple population spikes. 3. The (-)-isomer of PN 200-100 did not affect ethanol withdrawal hyperexcitability in the slices. 4. Neither isomer of PN 200-110 affected the field potentials in slices from control animals. 5. The gamma-aminobutyric acid (GABA) antagonist, bicuculline, lowered thresholds for eliciting population spikes in hippocampal slices from untreated animals. The active, (+)-isomer of PN 200-110 did not affect this action of bicuculline in hippocampal slices from untreated animals. 6. The stereoisomerism of the action of PN 200-110 on ethanol withdrawal hyperexcitability in the hippocampal slice was therefore the same as that seen in blockade of calcium channels. The results suggested that ethanol withdrawal hyperexcitability recorded in the isolated hippocampal slice involved increased activity of voltage-sensitive calcium channels.
Whittington
M A
MA
Pharmacology Department, Medical School, Bristol.
Little
H J
HJ
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017275:Isradipine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010069:Oxadiazoles / Q000494:pharmacology; D012044:Regression Analysis; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D000431:Ethanol; D001640:Bicuculline; D017275:Isradipine