CPP and amlodipine alter the decrease in basal acetylcholine and choline release by audiogenic stimulus in hippocampus of ethanol-withdrawn rats in vivo.
Effects of N-methyl-D-aspartate (NMDA) receptor and Ca2+ channel antagonists on extracellular acetylcholine and choline release in the hippocampus of ethanol-withdrawn rats were investigated by in vivo microdialysis. Ethanol was administered to Wistar rats in a liquid diet for 28 days. Basal acetylcholine and choline levels significantly increased at the 24th hour of ethanol withdrawal syndrome (EWS). Either an NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or a calcium channel antagonist amlodipine was administered, and 15 min later, an audiogenic stimulus (100 dB, 1 min) was applied to rats. While audiogenic stimulus increased acetylcholine and had no effect on choline release in control rats, it decreased acetylcholine and increased choline release in ethanol-withdrawn rats. CPP (15 mg/kg) and amlodipine (20 mg/kg) reversed the decrement in acetylcholine and increment in choline release in EW rats. Their effects on acetylcholine and choline release were not different from saline in control rats. Therefore, our findings suggest that, (a) because of adaptive changes in EWS, decrease of the acetylcholine release following audiogenic stimulus may play a role in the triggering of seizures, (b) hippocampal glutamatergic pathway may play a role in the audiogenic stimulus induced decrement of acetylcholine release in EWS, (c) inhibition of this pathway by NMDA receptor and calcium channel antagonists may prevent triggering of the seizures.
Department of Medical Pharmacology, Psychopharmacology Research Unit, Gülhane Military Medical Academy, Etlik 06018, Ankara, Turkey. tcelik@gata.edu.tr
Turgay
T
Celik
Hakan
H
Kayir
Mert
M
Ceyhan
Serdar
S
Demirtaş
Ahmet
A
Coşar
I Tayfun
IT
Uzbay
D000109:Acetylcholine / Q000378:metabolism*; D000161:Acoustic Stimulation / Q000009:adverse effects; D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D020195:Epilepsy, Reflex / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D000431:Ethanol / Q000009:adverse effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D010879:Piperazines; D017311:Amlodipine; D000431:Ethanol; D018698:Glutamic Acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D002794:Choline; D000109:Acetylcholine