The ethanol metabolite acetaldehyde inhibits the induction of long-term potentiation in the rat dentate gyrus in vivo.
1. Ethanol has been reported to inhibit the induction of long-term potentiation (LTP) in the hippocampus. However, the correlation between the effects of ethanol in vivo and in vitro remained unclear. In addition, previous works have little considered the possibility that the effect of ethanol is mediated by its metabolites. To solve these problems, we investigated the effects of ethanol and acetaldehyde, the first metabolite in the metabolism of ethanol, on the induction of LTP at medial perforant path-granule cell synapses in the dentate gyrus of anaesthetized rats in vivo. 2. Oral administration of 1 g kg-1 ethanol significantly inhibited the induction of LTP, confirming the effectiveness of ethanol in vivo. 3. A lower dose of ethanol (0.5 g kg-1) failed to inhibit the induction of LTP in intact rats, but significantly inhibited LTP in rats treated with disulfiram, an inhibitor of aldehyde dehydrogenase, demonstrating that LTP is inhibited by acetaldehyde accumulation following ethanol administration. 4. Intravenous injection of acetaldehyde (0.06 g kg-1) significantly inhibited the induction of LTP. 5. The inhibitory effect of acetaldehyde on LTP induction was also observed when it was injected into the cerebroventricules, suggesting that acetaldehyde has a direct effect on the brain. The intracerebroventricular dose of acetaldehyde effective in inhibiting LTP induction (0.1 - 0.15 mg brain-1) was approximately 10 fold lower than that of ethanol (1.0 - 1.5 mg brain-1). 6. It is possible that acetaldehyde is partly responsible for memory impairments induced by ethanol intoxication.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. kazuhoab@mol.fu-toko.ac.jp
Yamaguchi
S
S
Sugiura
M
M
Saito
H
H
D000079:Acetaldehyde / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004221:Disulfiram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D000431:Ethanol; D000079:Acetaldehyde; D004221:Disulfiram