Ethanol withdrawal hyperexcitability in vivo and in isolated mouse hippocampal slices.
Withdrawal hyperexcitability was seen in isolated mouse hippocampal slices, prepared after chronic treatment with ethanol, by inhalation for 2 weeks. The pattern of hyperexcitability differed from those seen previously when a different method of ethanol administration and a different strain of mice were used. Thresholds for field potentials were decreased, but the transient increase in paired pulse potentiation, reported earlier, was not evident. Chronic administration of the calcium channel antagonist, isradipine (PN-200-110) during ethanol treatment significantly decreased the withdrawal syndrome, both in vivo and in vitro. Brain concentrations of isradipine during the test period were found to be sufficient to produce acute effects on the withdrawal hyperexcitability. No changes were seen in the field potentials when slices were prepared after treatment with isradipine alone. A small, but significant, increase in excitability was seen in vivo after the treatment with isradipine alone. Previous studies showed that isradipine did not protect against the hyperexcitability due to gamma-aminobutyric acid (GABA)A antagonism, so the results suggest that neuronal calcium channels may be involved in ethanol withdrawal hyperexcitability, but decreases in GABAA inhibition may not be important.
Ripley
T L
TL
Pharmacology Department, Medical School, University Walk, Bristol, UK.
Whittington
M A
MA
Butterworth
A R
AR
Little
H J
HJ
D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D017275:Isradipine / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011963:Receptors, GABA-A; D000431:Ethanol; D017275:Isradipine