Associate editor: A.L. MorrowLow dose acute alcohol effects on GABAA receptor subtypes
Section snippets
Introduction: attempts to identify the receptors for low dose alcohol action
Ethanol (EtOH) is by far the most widely used and abused drug and EtOH-related accidents and other problems caused by alcohol abuse and addiction cause tremendous human suffering. On the other hand, there is increasing evidence that controlled low to moderate EtOH consumption has a number of long-term positive health implications. These potential beneficial alcohol effects include lower rates of myocardial infarction, reduced heart failure rate, lower risk for dementia, decreased risk of
Early pharmacological evidence for the involvement of GABAA receptors in alcohol actions
GABAARs have long been implicated in the intoxicating actions of alcohol because positive modulators of GABAARs such as barbiturates show striking similarities to alcohol in their effects on human behavior (Isbell et al., 1950). In addition, it was demonstrated that the GABAAR agonists (e.g., muscimol) potentiated the sedative properties of EtOH, while the opposite effect, a reduction of EtOH-produced sedation or motor-incoordinating effects, was seen upon administration of the GABAAR blocking
Summary and future directions
GABAAR subtypes containing the δ subunit, in vivo most frequently associated with α4 or α6 subunits, show an extra- or perisynaptic location and unique physiology and pharmacology. These receptors mediate tonic currents in vivo, and in recombinant systems when expressed with the β3 subunit are sensitive to EtOH concentrations that mirror the blood alcohol concentrations achieved during low and moderate ethanol consumption. These highly EtOH-sensitive receptors are positioned in the CNS
Acknowledgments
This work was supported by a NIH pre-doctoral fellowship AA015460 to H.J.H., an Alcoholic Beverage Medical Research Foundation grant to M.W., NIH grants NS35985 and AA07680 and funds provided by the State of California for medical research on alcohol and substance abuse to R.W.O.
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2015, AlcoholCitation Excerpt :Therefore, alcohol-induced activation of GABAA receptors may result in sleep promotion. However, the effects of alcohol on GABAA receptors are complex and not clearly understood [reviewed in Aguayo, Peoples, Yeh, & Yevenes, 2002; Siggins, Roberto, & Nie, 2005; Wallner et al., 2006]. In addition, recent reports suggest that the intoxicating effects of alcohol may be due to activation of extrasynaptic δ subunit-containing GABAA receptors (Breese et al., 2006; Wallner et al., 2006).