Benzodiazepines as antidepressants: Does GABA play a role in depression?

Petty, Frederick; Trivedi, Madhukar H.; Fulton, Mark; Rush, A. John

doi:10.1016/0006-3223(95)00049-7

Cited by 128 publications

(75 citation statements)

References 52 publications

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“…216,270 However, these drugs involve several neurotransmitter systems, such as serotonergic, monoaminergic, and GABAergic systems. 33,44,54 Petty argued 87,282 that GABAergic transmission may mediate noradrenergic function in a unified concept of antidepressant mechanism of action that is complement to the noradrenergic theory of mood disorder. Based on this hypothesis and on the modulation of monoaminergic and serotonergic systems by GABAergic pathways, it is possible to speculate that low basal GABA level may lead to reduced level of monoaminergic and serotonergic transmissions.…”

Section: Discussionmentioning

confidence: 99%

GABAergic dysfunction in mood disorders

et al. 2003

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Section: Discussionmentioning

confidence: 99%

GABAergic dysfunction in mood disorders

et al. 2003

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“…Some benzodiazepines have also been shown to have antidepressant activity in humans (Amsterdam et al, 1986;Petty et al, 1995), but their sedative action largely precludes testing them in tasks of pharmacological predictability of antidepressant-like responses (also referred to as tests of behavioral despair like the FST and the TST). Thus, we conducted tests to evaluate whether modulation of specific GABA A receptor subtypes, which do not cause sedation (α2, α3, and α5), may lead to antidepressant-like effects in the FST and the TST.…”

Section: Tests Of Predictive Validity Of Antidepressant-like Responsementioning

confidence: 99%

A Pharmacogenetic ‘Restriction-of-Function’ Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by α5-Containing GABAA Receptors in Mice

Behlke

Foster

Liu

et al. 2016

Neuropsychopharmacol

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Benzodiazepines have been widely used for their anxiolytic actions. However, the contribution of GABA A receptor subtypes to anxiolysis is still controversial. Studies with mutant mice harboring diazepam-insensitive α-subunits α1, α2, α3, or α5 have revealed that α2-containing GABA A receptors (α2-GABA A Rs) are required for diazepam-induced anxiolysis, with no evidence for an involvement of any other α-subunit, whereas TP003, described as a selective modulator of α3-containing GABA A receptors, was shown to be anxiolytic. Here, we describe a novel, systematic approach to evaluate the role of positive allosteric modulation of each of the four diazepam-sensitive α-subtypes in anxiety-related behavioral paradigms. By combining H to R point mutations in three out of the four diazepam-sensitive α-subunits in mice with a 129X1/SvJ background, diazepam becomes a subtype-specific modulator of the remaining non-mutated α-subtype. Modulation of α5-GABA A Rs, but not of α2-GABA A Rs, increased the time in the light side of the light-dark box as well as openarm exploration in the elevated plus maze. In contrast, modulation of α3-GABA A Rs decreased open-arm exploration, whereas modulation of α2-GABA A Rs increased time in the center in the open-field test. Modulation of any single α-subtype had no effect on stress-induced hyperthermia. Our results provide evidence that modulation of α5-GABA A Rs elicits anxiolytic-like actions, whereas our data do not provide evidence for an anxiolytic-like action of α3-GABA A Rs. Thus, α5-GABA A Rs may be suitable targets for novel anxiolytic drugs.

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“…Since anxiety is often accompanied by depression it is suggested that alprazolam is a more powerful anxiolytic in comparison to other benzodiazepines that lack these antidepressant properties (Petty et al 1995). The drug has a fast onset to anxiety relief (less than one week) when compared with anxiety treatment with buspirone or SSRIs (two to four weeks).…”

mentioning

confidence: 99%