Profound stress-induced alterations in flurazepam's antiseizure efficacy can be attenuated

Deutsch, Stephen I.; Rosse, Richard B.; Huntzinger, James A.; Novitzki, Monica R.; Mastropaolo, John

doi:10.1016/0006-8993(90)91715-s

Cited by 25 publications

(5 citation statements)

References 18 publications

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“…However, injection with pregnanolone or P 4 before the shock reinstated the acute anxiolytic-like effects of these compounds when administered 24 h later. These results are similar to the reduction in the anticonvulsant efficacy of flurazepam observed in mice 24 h after exposure to a cold water swim (Mastropaolo et al 1992), and that injection with flumazenil before the stress decreased the reduction in flurazepam's anticonvulsant efficacy (Deutsch et al 1990). Thus, potentiation of GABA A receptor-mediated function by BZs or neuroactive steroids before a stressor not only prevent the anxiogenic-like effects of stressors, but also rescue the anxiolytic-like activity of these compounds after the stressful experience.…”

Section: Discussionsupporting

confidence: 81%

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat

2000

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Section: Discussionsupporting

confidence: 81%

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat

2000

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“…In addition, colder water temperatures (Pericic et al, 2001) and longer swim durations (Abel and Berman, 1993) further increased resistance to seizures induced with GABA-related chemiconvulsants. However, swim stress does not seem to increase thresholds when seizures are induced using mechanisms that are GABA unrelated, and in fact, it exacerbates the response to electrically induced seizures (De Lima and Rae, 1991;Deutsch et al, 1990). Adding further variability, Pericic and Bujas (1997) showed that the anticonvulsive effects of swim stress were sex dependent, with females receiving the most protection.…”

Section: Acute Stress and Seizuresmentioning

confidence: 92%

Stress and Epilepsy: Multiple Models, Multiple Outcomes

Sawyer

Escayg

2010

Journal of Clinical Neurophysiology

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Human studies show a link between stress and epilepsy, with stress causing an increase in seizure frequency and severity in patients with epilepsy. Many different animal model systems have been used to better understand this connection and the possible mechanisms involved. This review highlights the results of such studies relating stress and seizure susceptibility, with a focus on the hypothalamic-pituitary-adrenal axis and its relationship to seizure generation. The effects of hypothalamic-pituitary-adrenal axis mediators, acute stress, chronic stress, and early life stress on the seizure phenotype are summarized. Results suggest that stress has both anticonvulsive and proconvulsive properties, depending on the animal strain and the stress/seizure induction paradigm used. Attempts to interpret the stress-epilepsy literature must take these variables into account. The growing availability of genetically modified mice that carry either human epilepsy mutations or mutations in stress pathway genes now provide the opportunity to examine the relationship between stress and epilepsy more directly.

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“…In males, forced swim stress has been observed to remove anxiolytic effects of diazepam on the dark–light exploratory behavior test (Briones‐Aranda et al. 2005), reduce the antiseizure efficacy of benzodiazepines (Deutsch et al. 1990), and reduce the seizure‐threshold for bicuculline and picrotoxin (Soubrie et al.…”

Section: Acute Stress and Gabaa Receptorsmentioning

confidence: 99%

“…Also consistent with stress-induced changes in GABA A receptor sensitivity and binding site number are studies showing that acute stress alters behavioral sensitivities to GABA A receptor ligands. In males, forced swim stress has been observed to remove anxiolytic effects of diazepam on the dark-light exploratory behavior test (Briones-Aranda et al 2005), reduce the antiseizure efficacy of benzodiazepines (Deutsch et al 1990), and reduce the seizure-threshold for bicuculline and picrotoxin (Soubrie et al 1980;Drugan et al 1985;Abel and Berman 1993;Pericic et al 2001). These findings suggest altered sensitivity of GABA A receptors to these compounds.…”

Section: Effects Of Acute Stress On Gaba a Receptor Allosteric Bindinmentioning

confidence: 99%

Stress and GABA_A receptors

Skilbeck

Johnston

Hinton

2010

Journal of Neurochemistry

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GABA A receptors are sensitive to subtle changes in the environment in both early-life and adulthood. These neurochemical responses to stress in adulthood are sex-dependent. Acute stress induces rapid changes in GABA A receptors in experimental animals, with the direction of the changes varying according to the sex of the animals and the stress-paradigm studied. These rapid alterations are of particular interest as they provide an example of fast neurotransmitter system plasticity that may be mediated by stress-induced increases in neurosteroids, perhaps via effects on phosphorylation and/or receptor trafficking. Interestingly, some studies have also provided evidence for long-lasting changes in GABA A receptors as a result of exposure to stressors in early-life. The short-and long-term stress sensitivity of the GABAergic system implicates GABA A receptors in the non-genetic etiology of psychiatric illnesses such as depression and schizophrenia in which stress may be an important factor. Keywords: depression, development, GABA A receptor, schizophrenia, sex differences, stress. 1999), particularly in the ratio 2 : 2 : 1, although stoichiometry may vary (i.e. 2 : 1 : 2, 3 : 2 : 0) . Different receptor subtypes vary in their pharmacological sensitivities, channel kinetics as well as their ontogenic, regional, and cellular distributions. Of recent interest is the different composition of GABA A receptors located at synaptic compared with extrasynaptic sites (Belelli et al. 2009). For example, receptors containing c 2 subunits are predominantly clustered in synaptic locations, while receptors containing d subunits are generally diffusely located at extrasynaptic sites (Essrich et al. 1998;Jacob et al. 2008). Receptors at extrasynaptic sites provide tonic inhibition as demonstrated by the slow decay kinetics and high affinity for GABA of d-subunit containing GABA A receptors, allowing for sensitivity to GABA that spills over from the synapse (Saxena and Macdonald 1994;Banks et al. 2000). This tonic inhibition appears to serve an important role in brain function given that d-subunit knockout mice display spontaneous seizures indicative of a drastic loss of inhibitory tone (Mihalek et al. 1999). GABA A receptor pharmacologyThe orthosteric site The orthosteric site of GABA A receptors is the site where GABA binds to induce chloride channel opening and membrane currents. The orthosteric site is selectively blocked by the antagonist bicuculline but no selective GABA A receptor agonist exists that does not act on GABA B or GABA C receptors (Johnston 2005). For example, muscimol acts as a bicuculline-sensitive agonist at GABA A receptor orthosteric sites but also acts as a more potent bicuculline-insensitive agonist at GABA C receptors (Johnston 2005). High-and low-affinity binding sitesThe orthosteric binding site has been extensively studied using radiolabeled agonists such as [ . Analysis of Scatchard's plots from such studies has lead to a general consensus that there exist both high-affinity (nM) and low-affin...

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Profound stress-induced alterations in flurazepam's antiseizure efficacy can be attenuated

Cited by 25 publications

References 18 publications

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat

Stress and Epilepsy: Multiple Models, Multiple Outcomes

Stress and GABA_A receptors

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Profound stress-induced alterations in flurazepam's antiseizure efficacy can be attenuated

Cited by 25 publications

References 18 publications

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat

Stress and Epilepsy: Multiple Models, Multiple Outcomes

Stress and GABAA receptors

Contact Info

Product

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Stress and GABA_A receptors