ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Differential roles of GABA(A) receptor subtypes in benzodiazepine-induced enhancement of brain-stimulation reward.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
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- Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAFrontiers in neuroscience · 2020Review
- TPA-023 attenuates subchronic phencyclidine-induced declarative and reversal learning deficits via GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
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- GABRA2, alcohol, and illicit drug use: An event-level model of genetic risk for polysubstance use.Journal of abnormal psychology · 2018Article
- Abuse-related effects of subtype-selective GABAPsychopharmacology · 2017Article
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- A Pharmacogenetic 'Restriction-of-Function' Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by α5-Containing GABAA Receptors in Mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- The Role of Benzodiazepines in the Treatment of Epilepsy.Current treatment options in neurology · 2016Article
- α2-containing GABA(A) receptors: a requirement for midazolam-escalated aggression and social approach in mice.Psychopharmacology · 2015Article
- Molecular Genetic Testing in Pain and Addiction: Facts, Fiction and Clinical Utility.Addiction genetics · 2015Article
- Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype.Nature communications · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Benzodiazepines such as diazepam are widely prescribed as anxiolytics and sleep aids. Continued use of benzodiazepines, however, can lead to addiction in vulnerable individuals. Here, we investigate the neural mechanisms of the behavioral effects of benzodiazepines using the intracranial self-stimulation (ICSS) test, a procedure with which the reward-enhancing effects of these drugs can be measured. Benzodiazepines bind nonselectively to several different GABA(A) receptor subtypes. To elucidate the α subunit(s) responsible for the reward-enhancing effects of benzodiazepines, we examined mice carrying a histidine-to-arginine point mutation in the α1, α2, or α3 subunit, which renders the targeted subunit nonresponsive to diazepam, other benzodiazepines and zolpidem. In wild-type and α1-point-mutated mice, diazepam caused a dose-dependent reduction in ICSS thresholds (reflecting a reward-enhancing effect) that is comparable to the reduction observed following cocaine administration. This effect was abolished in α2- and α3-point-mutant mice, suggesting that these subunits are necessary for the reward-enhancing action of diazepam. α2 Subunits appear to be particularly important, since diazepam increased ICSS thresholds (reflecting an aversive-like effect) in α2-point-mutant animals. Zolpidem, an α1-preferring benzodiazepine-site agonist, had no reward-enhancing effects in any genotype. Our findings implicate α2 and α3 subunit containing GABA(A) receptors as key mediators of the reward-related effects of benzodiazepines. This finding has important implications for the development of new medications that retain the therapeutic effects of benzodiazepines but lack abuse liability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.