Ethanol and the GABA receptor complex: studies with the partial inverse benzodiazepine receptor agonist Ro 15-4513.
- Authors
- Glowa, J R; Crawley, J; Suzdak, P D; Paul, S M
- Year
- 1988
- Journal
- Pharmacology, biochemistry, and behavior
- PMID
- 2855121
- DOI
- 10.1016/0091-3057(88)90263-8
Ethanol potentiates GABA-receptor-mediated Cl- ion flux in vitro and, at similar concentrations, has anxiolytic and intoxicating properties in vivo. The imidazobenzodiazepine, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-meth-6-oxo-4H- imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate), is a potent partial inverse agonist of the benzodiazepine/GABA receptor which can antagonize the in vitro actions of ethanol in potentiating GABA receptor-mediated Cl- ion flux. Moreover, several of the behavioral effects of ethanol are also antagonized by Ro 15-4513, and these effects can be demonstrated in several paradigms at doses of Ro 15-4513 that do not produce opposite behavioral effects. In contrast, in our studies, other benzodiazepine receptor antagonist and inverse agonists, including Ro 15-1788, FG-7142, and beta-CCE were not able to antagonize these biochemical or behavioral effects of ethanol at doses that were without intrinsic effects. However, both Ro 15-1788 and beta-CCE blocked the antagonism of ethanol's effects by Ro 15-4513, suggesting a role for the GABA receptor complex in the actions of ethanol. These studies provide further evidence that GABAergic neurones may mediate at least some of the behavioral and biochemical actions of low-to-moderate doses of ethanol.
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Interactions of alcohol and the benzodiazepine inverse agonist in healthy male volunteers. | Singh N et al. | β | 2025 | β |
| Sex Differences in the Expression of the Ξ±5 Subunit of the GABA<sub>A</sub> Receptor in Alcoholics with and without Cirrhosis of the Liver. | Janeczek P et al. | β | 2020 | β |
| Behavioral and neurobiological mechanisms of punishment: implications for psychiatric disorders. | Jean-Richard-Dit-Bressel P et al. | β | 2018 | β |
| GABAA receptors in the posterior, but not anterior, ventral tegmental area mediate Ro15-4513-induced attenuation of binge-like ethanol consumption in C57BL/6J female mice. | MelΓ³n LC et al. | β | 2011 | β |
| Ξ±4-Containing GABA(A) Receptors are Required for Antagonism of Ethanol-Induced Motor Incoordination and Hypnosis by the Imidazobenzodiazepine Ro15-4513. | Iyer SV et al. | β | 2011 | β |
| Genetics of addictions. | Hartz SM et al. | β | 2010 | β |
| Genetics of addictions. | Hartz SM et al. | β | 2010 | β |
| Antagonism of the ethanol-like discriminative stimulus effects of ethanol, pentobarbital, and midazolam in cynomolgus monkeys reveals involvement of specific GABA(A) receptor subtypes. | Helms CM et al. | β | 2009 | β |
| Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors. | Hanchar HJ et al. | β | 2006 | β |
| Low dose acute alcohol effects on GABA A receptor subtypes. | Wallner M et al. | β | 2006 | β |
| Low-dose alcohol actions on alpha4beta3delta GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513. | Wallner M et al. | β | 2006 | β |
| Role of GABAA alpha5-containing receptors in ethanol reward: the effects of targeted gene deletion, and a selective inverse agonist. | Stephens DN et al. | β | 2005 | β |
| GABAergic neurosteroid modulation of ethanol actions. | Khisti RT et al. | β | 2002 | β |
| Ethanol and neurosteroid interactions in the brain. | Morrow AL et al. | β | 2001 | β |
| The pharmacodynamics of anticonvulsant and subconvulsant effects of ethanol in CBA and C57BL/6 mice. | Zhuk OV et al. | β | 2001 | β |
| The role of GABAergic neuroactive steroids in ethanol action, tolerance and dependence. | Morrow AL et al. | β | 2001 | β |
| Neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one modulates electrophysiological and behavioral actions of ethanol. | VanDoren MJ et al. | β | 2000 | β |
| Effects of moderate alcohol consumption on the central nervous system. | Eckardt MJ et al. | β | 1998 | β |
| Alcohol, GABAA-benzodiazepine receptor complex, and aggression. | Miczek KA et al. | β | 1997 | β |
| Ro 15-4513 potentiates, instead of antagonizes, ethanol-induced sleep in mice exposed to small platform stress. | Pokk P et al. | β | 1996 | β |
| Use of 82Br- radiotracer to study transmembrane halide flux: the effect of a tranquilizing drug, chlordiazepoxide on channel opening of a GABAA receptor. | Cash DJ et al. | β | 1995 | β |
| Differential interactions between ethanol and Ro 15-4513 on two anxiety tests in rats. | Prunell M et al. | β | 1994 | β |
| Neurochemical correlates of sympathetic activation during severe alcohol withdrawal. | Hawley RJ et al. | β | 1994 | β |
| Prevention of the pro-aggressive effects of alcohol in rats and squirrel monkeys by benzodiazepine receptor antagonists. | Weerts EM et al. | β | 1993 | β |
| Pyridoxine therapy for ethanol toxicity? | Gallant DM | β | 1993 | β |
| The benzodiazepine receptor partial agonist bretazenil and the partial inverse agonist Ro 15-4513: effects on salt preference and aversion in the rat. | Cooper SJ et al. | β | 1993 | β |
| Effect of chronic ethanol treatment on the gamma-aminobutyric acid-mediated enhancement of [3H]flunitrazepam binding in rat cortex and hippocampus. | Negro M et al. | β | 1992 | β |
| Effect of Ro 15-4513 on ethanol-induced conditioned place preference. | Risinger FO et al. | β | 1992 | β |
| Effects of Ro 15-4513 and ethanol on operant behavior of male and female C57BL/6 mice. | Bao K et al. | β | 1992 | β |
| Pyridoxine acts in the brain to reduce ethanol toxicity in rats. | Gonzalez LE et al. | β | 1992 | β |
| Effects of Ro 15-4513 on ethanol discrimination in C57BL/6 mice. | Middaugh LD et al. | β | 1991 | β |
| RO15-4513 antagonizes the anxiolytic effects of ethanol in a nonshock conflict task at doses devoid of anxiogenic activity. | Becker HC et al. | β | 1991 | β |
| Differential actions of RO 15-1788 and diazepam on poikilothermia, motor impairment and sleep produced by ethanol. | Paez X et al. | β | 1990 | β |
| Effect of ethanol on memory consolidation in mice: antagonism by the imidazobenzodiazepine Ro 15-4513 and decrement by familiarization with the environment. | Castellano C et al. | β | 1990 | β |
| Effects of ethanol and Ro 15-4513 in an electrophysiological model of anxiolytic action. | Coop CF et al. | β | 1990 | β |
| The effects of Ro 15-4513 on ethanol-induced taste aversions. | Jeffreys RD et al. | β | 1990 | β |
| Alcohol-induced poikilothermia, sleep and motor impairment: actions on brain of EGTA and verapamil. | Paez X et al. | β | 1989 | β |
| Antagonizing the behavioural effects of drugs: a discussion with specific reference to benzodiazepines and alcohol. | Lister RG | β | 1989 | β |