Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex

Ferreri, María Celeste; Gutiérrez, María Laura; Gravielle, Marı́a Clara

doi:10.1016/j.neuroscience.2015.09.038

Cited by 30 publications

(17 citation statements)

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“…Tolerance to BZ diverse effects (i.e. sedative effects, motor disturbances or anxiolytic effects) after a prolonged treatment is a well-documented issue, demonstrated in many animal studies (Ferreri et al 2015; Talarek et al 2008; Talarek et al 2010; Vinkers and Olivier 2012). However, this diminution in the response to the drug does not occur simultaneously for every pharmacological property.…”

Section: Discussionmentioning

confidence: 99%

“…Tolerance to the sedative effects of BZ occurs more rapidly than to anticonvulsant effects, with the anxiolytic effects in animals at least, occurring after an even longer time period (Bateson 2002; Ferreri et al 2015; Gravielle 2016; Vinkers and Olivier 2012). These observations suggest that different mechanisms are responsible for the development of tolerance to each of these drug-induced effects and/or different brain regions and BZ receptor subunits are involved in these mechanisms (Bateson 2002; Ferreri et al 2015; Gravielle 2016). Furthermore, emergence of tolerance to BZ appears to be dependent on the route of drug administration, animal test studied and treatment schedule.…”

Section: Discussionmentioning

confidence: 99%

“…This group of agents is widely used in clinics, but the use of these compounds is limited by the development of tolerance to most of their pharmacological actions that occurs after prolonged administration (Bateson 2002; Ferreri et al 2015; Gravielle 2016). …”

Section: Introductionmentioning

confidence: 99%

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The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

et al. 2016

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The goal of the study was to investigate the effects of drugs modifying l-arginine:NO:cGMP pathway on the development of tolerance to flunitrazepam (FNZ)-induced motor impairment in mice. FNZ-induced motor incoordination was assessed on the 1st and 8th days of experiment, using the rotarod and chimney tests. It was found that (a) both a non-selective nitric oxide synthase (NOS) inhibitor: N G-nitro-l-arginine methyl ester (l-NAME) and an unselective neuronal NOS inhibitor: 7-nitroindazole (7-NI) inhibited the development of tolerance to the motor-impairing effects of FNZ in the rotarod and the chimney tests and (b) both a NO precursor: l-arginine and a selective inhibitor of phosphodiesterase 5 (PDE5): sildenafil did not affect the development of tolerance to FNZ-induced motor impairment in mice. Those findings provided behavioural evidence that NO could contribute an important role in the development of tolerance to FNZ in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

et al. 2016

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“…49) Antianxiety treatment is effective in lowering blood pressure in patients with excessive hypertension. 50) The clinical use of benzodiazepines is limited by the development of tolerance to their pharmacological effects. 51) AGII is primarily involved in the inflammatory process by modulating cytokine release and proinflammatory transcription factors such as NF-κB.…”

Section: Discussionmentioning

confidence: 99%

Effect of <i>Ocimum basilicum</i>, <i>Ocimum selloi</i>, and Rosmarinic Acid on Cerebral Vascular Damage in a Chronic Hypertension Model

Alegría-Herrera

Herrera-Ruíz

Román-Ramos

et al. 2019

Biological & Pharmaceutical Bulletin

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The main objective of treatment against hypertension is not only to reduce blood pressure levels, but also to reduce vascular risk in general. In the present work, administering angiotensin II (AGII; 0.2 µg/kg intraperitoneally (i.p.) for 12 weeks) activates the hypothalamic-pituitary-adrenal (HPA) axis, which caused an increase in corticosterone levels, as well as in proinflammatory cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α)) and macrophage chemotactic protein 1 (MCP-1), and decreased anti-inflammatory cytokines (interleukin 10 (IL-10) and interleukin 4 (IL-4)). On observing the behavior in the different models, an anxiogenic effect (elevated plus maze (EPM)) and cognitive impairment (water Morris maze (WMM)) was observed in animals with AGII. By administering organic extracts from Ocimum basilicum (Oba-EtOAc) and Ocimum selloi (Ose-EtOAc), and some doses of rosmarinic acid (RA) (6 weeks per os (p.o.)), the damage caused by AGII was stopped by re-establishing corticosterone serum levels and by decreasing the proinflammatory cytokines and MCP-1.

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“…Nevertheless, many studies have focused on changes to the receptor following sustained activation with agonists or allosteric modulators 17 . These changes include: phosphorylation of receptor subunits [18][19][20][21] , altered expression of GABAARs 18,21-28 , changes to receptor mobility and clustering 26,[29][30][31] , and alterations to receptor pharmacology 32 .…”

Section: Introductionmentioning

confidence: 99%

A physiological role for GABA_Areceptor desensitization – induction of long-term potentiation at inhibitory synapses

Field

Thomas

Smart

2020

Preprint

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GABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission. AbbreviationsANOVA, analysis of variance; Bis, bisindolylmalemide-I; CNS, central nervous system; Eto, etomidate; GABA, γ-aminobutyric acid; GABAAR, γ-aminobutyric acid receptor type A; HEK, human embryonic kidney cell line 293; IEI, inter-event interval; iLTP, inhibitory long-term potentiation; mIPSC, mini-inhibitory postsynaptic current; PKC, protein kinase C; PLC, phospholipase c; pLGIC, pentameric ligand-gated ion channel; PMA, phorbol 12-myristate 13-acetate; PS, pregnenolone sulfate; Ptx, picrotoxin; sIPSC, spontaneous inhibitory postsynaptic current; t-SNE, t-distributed stochastic neighbour embedding; TTX, tetrodotoxin. AcknowledgementsThis work was supported by an MRC programme grant (TGS). MF was supported by a 4year MRC Postgraduate Studentship. Author contributionsMF performed electrophysiology, biochemical and molecular experiments and associated analyses, and contributed significantly towards directing the study; PT performed electrophysiology experiments and analysis and advised on project direction; TGS conceived the study, supervised the study's direction and provided resources. All authors contributed towards the writing, editing and reviewing of the paper.

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Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex

Cited by 30 publications

References 34 publications

The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

Effect of <i>Ocimum basilicum</i>, <i>Ocimum selloi</i>, and Rosmarinic Acid on Cerebral Vascular Damage in a Chronic Hypertension Model

A physiological role for GABA_Areceptor desensitization – induction of long-term potentiation at inhibitory synapses

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Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex

Cited by 30 publications

References 34 publications

The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

Effect of <i>Ocimum basilicum</i>, <i>Ocimum selloi</i>, and Rosmarinic Acid on Cerebral Vascular Damage in a Chronic Hypertension Model

A physiological role for GABAAreceptor desensitization – induction of long-term potentiation at inhibitory synapses

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A physiological role for GABA_Areceptor desensitization – induction of long-term potentiation at inhibitory synapses