The ethanol metabolite acetaldehyde inhibits the induction of long‐term potentiation in the rat dentate gyrus in vivo

Abstract

1 Ethanol has been reported to inhibit the induction of long-term potentiation (LTP) in the hippocampus. However, the correlation between the e ects of ethanol in vivo and in vitro remained unclear. In addition, previous works have little considered the possibility that the e ect of ethanol is mediated by its metabolites. To solve these problems, we investigated the e ects of ethanol and acetaldehyde, the ®rst 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 71 ethanol signi®cantly inhibited the induction of LTP, con®rming the e ectiveness of ethanol in vivo. 3 A lower dose of ethanol (0.5 g kg 71 ) failed to inhibit the induction of LTP in intact rats, but signi®cantly inhibited LTP in rats treated with disul®ram, 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 71 ) signi®cantly inhibited the induction of LTP. 5 The inhibitory e ect of acetaldehyde on LTP induction was also observed when it was injected into the cerebroventricules, suggesting that acetaldehyde has a direct e ect on the brain. The intracerebroventricular dose of acetaldehyde e ective in inhibiting LTP induction (0.1 ± 0.15 mg brain 71 ) was approximately 10 fold lower than that of ethanol (1.0 ± 1.5 mg brain 71 ). 6 It is possible that acetaldehyde is partly responsible for memory impairments induced by ethanol intoxication.

Acute and chronic effects of ethanol on learning-related synaptic plasticity

“…The brain expresses several ADH variants (Galter, Carmine, Buervenich, Duester, & Olson, 2003), and hippocampal pyramidal neurons have a variant with low ethanol affinity (Haseba & Ohno, 2010; Mori et al, 2000), consistent with the requirement for high concentrations for effects on LTP and neurosteroids. These findings are also consistent with prior studies demonstrating that acetaldehyde can serve as a trigger for neurosteroid synthesis (Boyd, O’Buckley, & Morrow, 2008), and that an inhibitor of aldehyde dehydrogenase facilitates ethanol’s block of LTP in the dentate gyrus in vivo (Abe, Yamaguchi, Sugiura, & Saito, 1999). …”

Ethanol Enhances Reactivated Fear Memories

“…Second, some metabolites of ethanol (eg, acetaldehyde) are involved in the memory enhancement. Acetaldehyde, the first metabolite in the metabolism of ethanol, is partly responsible for inhibitory effects induced by ethanol (Abe et al, 1999).…”

Does Acetaldehyde Mediate Ethanol Action in the Central Nervous System?

“…Thus, acetaldehyde might be expected to alter the function of NMDA or GABA A (or perhaps AMPA) receptors, but this was not the case with the combination of subunits that we examined. Perhaps a prolonged exposure would reveal changes in GABA A or glutamate receptor function consistent with acetaldehyde-mediated changes in LTP (Abe et al, 1999).…”