Effect of Ro 15-4513 and nifedipine on the behaviour and potassium-evoked calcium uptake following withdrawal from chronic ethanol administration in rats.
The termination of chronic ethanol administration in rats resulted in the development of withdrawal signs at 10 and 24 hours of withdrawal. The behavioural signs of withdrawal were accompanied by an increased potassium-evoked 45Ca2+ uptake by cortical synaptoneurosomes. The dihydropyridine calcium channel antagonist nifedipine given acutely, suppressed the withdrawal signs and abolished the increased 45Ca2+ uptake. The benzodiazepine receptor inverse agonist Ro 15-4513 (4 mg/kg) given at 1.5 hours after termination of chronic ethanol induced behavioural signs of withdrawal and increased potassium-evoked 45Ca2+ uptake in these animals. Ro 15-45-13 given at 24 hours of withdrawal did not further enhance withdrawal signs or 45Ca2+ uptake. These data suggest that an increased calcium uptake during ethanol withdrawal might be attributed to the activation of dihydropyridine-sensitive calcium channels and might be involved in the development of withdrawal signs after chronic ethanol administration.
Zharkovsky
A
A
Department of Pharmacology, Tartu University, Estonia.
Cebers
G
G
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001386:Azides; D015220:Calcium Channels; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513; D009543:Nifedipine; D011188:Potassium; D002118:Calcium