Antidepressant and anxiolytic effects of alprazolam versus the conventional. antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats

Flugý, A.; Gagliano, M.; Cannizzaro, Carla; Novara, V.; G, Cannizzaro

doi:10.1016/0014-2999(92)90123-l

Cited by 50 publications

(16 citation statements)

References 35 publications

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“…For mice, the forced-swimming conditions used in this test resemble more closely the situation of swimming-stress (once the animal does not touches the bottom with its hind paws) and in these conditions drugs like diazepam have the ability to increase immobility time [62,63] just as it was observed in our assay. Other structurally related compounds like apigenin, upon acute treatment with relatively high doses (25 mg/kg), have induced an antidepressant-like activity (reduction in immobility time) in the forced-swimming test [64].…”

Section: Discussionmentioning

confidence: 81%

Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity

Coleta

Campos

Cotrim

et al. 2008

Behavioural Brain Research

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Since the discovery that certain flavonoids (namely flavones) specifically recognise the central BDZ receptors, several efforts have been made to identify naturally occurring GABA A receptor benzodiazepine binding site ligands. Flavonoid derivatives with a flavone-like structure such as apigenin, chrysin and wogonin have been reported for their anxiolytic-like activity in different animal models of anxiety. Luteolin (3 ,4 ,5,7-tetrahydroxyflavone) is a widespread flavonoid aglycon that was reported as devoid of specific affinity for benzodiazepine receptor (BDZ-R) binding site, but its psychopharmacological activity is presently unknown. Considering (1) the close structural similarity with other active flavones, (2) the activity of some of its glycosilated derivatives and (3) the complexity of flavonoid effects in the central nervous system, luteolin was submitted to a battery of tests designed to evaluate its possible activity upon the CNS and its ability to interact with the BDZ-receptor binding sites was also analysed.Luteolin apparently has CNS activity with anxiolytic-like effects despite the low affinity for the BDZ-R shown in vitro. Our findings suggest a possible interaction with other neurotransmitter systems but we cannot rule out the possibility that luteolin's metabolites might show a higher affinity for the BDZ-R in vivo, thus eliciting the evident anxiolytic-like effects through a GABAergic mechanism.

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Section: Discussionmentioning

confidence: 81%

Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity

Coleta

Campos

Cotrim

et al. 2008

Behavioural Brain Research

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“…This extinction of locomotor impairment might result from the decreasing concentration of the ligand in the brain over time, leading to reduced α1 potentiation and reduced side effects on locomotion, as this particular compound displays high potency at α1-GABAA-R. For comparison, GL-II-73 affinity for α1-GABAA-Rs is exceptionally low, profoundly decreasing the propensity to elicit motor impairment. In contrast, DZP increased the time spent immobile, confirming its lack of antidepressant effect, or suggesting it induces a depressant-like state [43, 44], although this was probably confounded by motor-impairing effects. Clearly, all three ligands differ from DZP, although the extent of these putative antidepressant effects will need to be confirmed using CS or genetic rodent models.…”

Section: Discussionmentioning

confidence: 99%

Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles

Prevot¹,

Vidojević

et al. 2019

Complex Psychiatry

124

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Altered gamma-aminobutyric acid (GABA) function is consistently reported in psychiatric disorders, normal aging, and neurodegenerative disorders and reduced function of GABA interneurons is associated with both mood and cognitive symptoms. Benzodiazepines (BZ) have broad anxiolytic, but also sedative, anticonvulsant and amnesic effects, due to nonspecific GABA-A receptor (GABAA-R) targeting. Varying the profile of activity of BZs at GABAA-Rs is predicted to uncover additional therapeutic potential. We synthesized four novel imidazobenzodiazepine (IBZD) amide ligands and tested them for positive allosteric modulation at multiple α-GABAA-R (α-positive allosteric modulators), pharmacokinetic properties, as well as anxiolytic and antidepressant activities in adult mice. Efficacy at reversing stress-induced or age-related working memory deficits was assessed using a spontaneous alternation task. Diazepam (DZP) was used as a control. Three ligands (GL-II-73, GL-II-74, and GL-II-75) demonstrated adequate brain penetration and showed predictive anxiolytic and antidepressant efficacies. GL-II-73 and GL-II-75 significantly reversed stress-induced and age-related working memory deficits. In contrast, DZP displayed anxiolytic but no antidepressant effects or effects on working memory. We demonstrate distinct profiles of anxiolytic, antidepressant, and/or pro-cognitive activities of newly designed IBZD amide ligands, suggesting novel therapeutic potential for IBZD derivatives in depression and aging.

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“…The behavioral profile in this model, which has been termed ''behavioral despair,'' is characterized by a shift from active to passive behavior and has been thought to model some aspects of affective disorders (27)(28)(29). Importantly, a role for GABAR in these behaviors has been implicated by actions of BZs, which potentiate those of antidepressants in this model (30). Rats were subjected to the forced swim at least 2 wk after the Morris water maze.…”

Section: Slot-blot Preparation and Expression Profilesmentioning

confidence: 99%

Repeated neonatal handling with maternal separation permanently alters hippocampal GABA _A receptors and behavioral stress responses

Hsu

Zhang²,

Raol³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

136

105

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Increasing evidence suggests that postnatal events, such as handling or maternal separation, can produce long-term changes in brain function. These are often expressed as changes in the profile of endocrine or behavioral responses to stress. Changes in ␥-aminobutyric acid type A receptors (GABARs), which mediate the majority of fast synaptic inhibition in adult brain, have been proposed as one potential mediator of these behavioral effects. In the current article, we use a combination of single-cell electrophysiology and antisense mRNA amplification to demonstrate permanent molecular and functional differences in GABARs within hippocampal dentate granule neurons after as few as two episodes of neonatal handling with brief maternal separation. Adult animals that as pups experienced handling with maternal separation maintained a more immature GABAR phenotype and exhibited increased activity in response to swim stress. These findings demonstrate the exquisite sensitivity of the developing GABAergic system to even subtle environmental manipulations and provide an unique molecular mechanism by which postnatal handling with maternal separation may alter stress-related behavior.development ͉ glucocorticoid ͉ dentate granule neurons ͉ patch clamping ͉ single-cell antisense mRNA amplification T he developing nervous system can be exquisitely sensitive to even minor perturbations in the environment. It has been recognized for decades that handling of neonatal rats could produce profound effects on later neuroendocrine and behavioral responses to stress (1, 2). Repetitive brief handling in neonatal rats has been shown to result in permanent alterations in hippocampal glucocorticoid (GC) receptors, decreased GC responses to stress in adulthood, and a relative protection against age-related hippocampal neuronal death and cognitive impairments (3). Adult animals handled as pups also demonstrate decreased expression of fear-related behaviors under stressful conditions (4-6). The molecular mechanisms underlying handling-induced behavioral and cognitive changes are not fully understood. ␥-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in mammalian brain and regulates both endocrine and behavioral responses to stress (7-9). Benzodiazepines (BZs) and other drugs that potentiate GABA currents can be potent anxiolytics. Rats exposed to early-life handling have been found to have altered BZ receptor levels in several brain regions including brainstem nuclei, amygdala, and frontal cortex (5, 6), but handling effects on GABA type A receptor (GABAR) subunit expression and function in hippocampal neurons have not, to our knowledge, previously been reported.GABARs are chloride ion channel-associated ligand-gated heteromeric receptors composed of five subunits, which are modulated by BZs, barbiturates, zinc, and neurosteroids. Many genetically distinct subunit subtypes, including ␣1-6, ␤1-4, ␥1-3, ␦, , , , and 1-3, have been identified (10, 11). GABARs can be assembled in different subunit combinations, resulting in a st...

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Antidepressant and anxiolytic effects of alprazolam versus the conventional. antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats

Cited by 50 publications

References 35 publications

Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity

Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity

Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles

Repeated neonatal handling with maternal separation permanently alters hippocampal GABA _A receptors and behavioral stress responses

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Antidepressant and anxiolytic effects of alprazolam versus the conventional. antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats

Cited by 50 publications

References 35 publications

Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity

Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity

Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles

Repeated neonatal handling with maternal separation permanently alters hippocampal GABA A receptors and behavioral stress responses

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Product

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Repeated neonatal handling with maternal separation permanently alters hippocampal GABA _A receptors and behavioral stress responses