The sedative but not the memory-blocking properties of ethanol are modulated by alpha 5-subunit-containing gamma -aminobutyric acid type A receptors

• Published in: Behavioural brain research Vol. 217; no. 2; pp. 379 - 385
• Main Authors: Martin, Loren J, Zurek, Agnieszka A, Bonin, Robert P, Oh, Gabriel HT, Kim, John H, Mount, Howard TJ, Orser, Beverley A
• Format: Journal Article
• Language: English
• Published: 01.03.2011
• ISSN: 0166-4328
• DOI: 10.1016/j.bbr.2010.11.008

The precise mechanisms underlying the memory-blocking properties of ethanol are unknown, in part because ethanol targets a wide array of neurotransmitter receptors and transporters. The aim of this study was to determine whether the memory loss caused by ethanol is mediated, in part, by alpha 5 subunit-containing gamma -aminobutyric acid subtype A receptors. These receptors have been implicated in learning and memory processes and are targets for a variety of neurodepressive drugs. Also, since these receptors generate a tonic inhibitory current in hippocampal pyramidal neurons, we examined whether concentrations of ethanol that block memory in vivo increased the tonic current using whole-cell patch-clamp recordings in hippocampal neurons. Null mutant mice lacking the alpha 5 subunit (Gabra5a degree /a degree ) and wild-type mice were equally impaired in contextual fear conditioning by moderate (1mg/kg) and high (1.5mg/kg) doses of ethanol. The higher dose of ethanol also reduced auditory delay fear conditioning to the same extent in the two genotypes. Interestingly, wild-type mice were more sensitive than Gabra5a degree /a degree mice to the sedative effects of low (0.5mg/kg) and moderate (1mg/kg) doses of ethanol in the open-field task. Concentrations of ethanol that impaired memory performance in vivo did not increase the amplitude of the tonic current. Together, the results suggest that the alpha 5-subunit containing gamma -aminobutyric acid subtype A receptors are not direct targets for positive modulation by ethanol nor do they contribute to ethanol-induced memory loss. In contrast, these receptors may contribute to the sedative properties of ethanol.