The Experts below are selected from a list of 108 Experts worldwide ranked by ideXlab platform
Elena Romeo - One of the best experts on this subject based on the ideXlab platform.
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Changes in CCK-4 induced panic after treatment with the GABA-reuptake inhibitor tiagabine are associated with an increase in 3α,5α-Tetrahydrodeoxycorticosterone concentrations
Psychoneuroendocrinology, 2009Co-Authors: P Zwanzger, D Eser, T C Baghai, F Padberg, Elena Romeo, Flavia Di Michele, Augusto Pasini, R RupprechtAbstract:Summary There is evidence that gamma-amino-butyric acid type A (GABA A )-receptor modulating neuroactive steroids play a role in the pathophysiology of panic disorder. Antidepressant treatment has been suggested to stabilize the concentrations of neuroactive steroids. In this pilot study we investigated neuroactive steroid concentrations during GABAergic treatment, which might represent an alternative anxiolytic pharmacotherapeutic strategy. Neuroactive steroid concentrations were determined in 10 healthy subjects treated with tiagabine. To evaluate the anxiolytic effects of tiagabine a cholecystokinine-tetrapeptide (CCK-4) challenge was performed before and after treatment. Treatment with tiagabine led to a significant increase in 3α,5α-Tetrahydrodeoxycorticosterone (3α,5α-THDOC) from 0.49 to 1.42 nmol/l ( Z = −2.80, p = .005), which was significantly correlated with a decrease of panic symptoms in the CCK-4 challenge. Thus, it might be hypothesized that the anxiolytic effects of GABAergic treatment might in part be mediated by their influence on 3α,5α-THDOC concentrations.
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mirtazapine does not influence Tetrahydrodeoxycorticosterone levels in depressed patients
World Journal of Biological Psychiatry, 2007Co-Authors: Cornelius Schule, T C Baghai, Elena Romeo, Flavia Di Michele, Augusto Pasini, Daniela Eser, Rainer RupprechtAbstract:Background. Among the neuroactive steroids, 3a,5a-Tetrahydrodeoxycorticosterone (3a,5a-THDOC) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA) system. The antidepressant mirtazapine has been shown to attenuate HPA axis activity and to increase the concentrations of 3a-reduced metabolites of progesterone in depressed patients. In the present study, the impact of mirtazapine on 3a,5aTHDOC levels was investigated in relation to clinical response in depressed patients. Method. A total of 23 drug-free inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 08:00 h and were quantified for 3a,5a-THDOC levels. Results. 3a,5aTHDOC levels were not correlated with demographic and clinical parameters such as age and severity of depression. Moreover, 5-week treatment with mirtazapine did not influence the 3a,5a-THDOC in the depressed patients, neither in responders nor in non-responders. Conclusion. Putative increasing effects of mirtazapine on 3a-reduced neuroactive steroids such as 3a,5a-THDOC which may be mediated via an impact on the neurosteroidogenic enzyme 3a-hydroxysteroid dehydrogenase seem to be counterbalanced by the mirtazapine-induced inhibition of ACTH secretion which directly influences the 3a,5a-THDOC release of the adrenal cortex.
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panic induction with cholecystokinin tetrapeptide cck 4 increases plasma concentrations of the neuroactive steroid 3 alpha 5 alpha Tetrahydrodeoxycorticosterone 3 alpha 5 alpha thdoc in healthy volunteers
Neuropsychopharmacology, 2005Co-Authors: Daniela Eser, P Zwanzger, T C Baghai, Flavia Di Michele, Augusto Pasini, Cornelius Schule, Rainer Rupprecht, Elena RomeoAbstract:3α-reduced neuroactive steroids such as 3α, 5α-tetrahydroprogesterone (3α, 5α-THP) and 3α, 5α-Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) are potent positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3α, 5α-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3α, 5α-THDOC concentrations during experimental panic induction. Therefore, we quantified 3α, 5α-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3α, 5α-THDOC, ACTH and cortisol concentrations. This increase in 3α, 5α-THDOC might be a consequence of hypothalamic–pituitary–adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.
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fluoxetine decreases concentrations of 3α 5α Tetrahydrodeoxycorticosterone thdoc in major depression
Journal of Psychiatric Research, 2000Co-Authors: Andreas Strohle, Elena Romeo, Augusto Pasini, B Hermann, Gianfranco Spalletta, F Di Michele, Florian Holsboer, Rainer RupprechtAbstract:There is evidence for a differential alteration in the concentrations of 3α-reduced neuroactive steroids in major depression. Because it has been suggested that fluoxetine may shift the activity of the 3α-hydroxysteroid oxidoreductase towards the reductive direction, treatment of major depression may be accompanied by a further increase in plasma 3α,5α-Tetrahydrodeoxycorticosterone (THDOC) concentration. We studied eight male depressed patients before and after treatment with fluoxetine and compared them to healthy age-matched control subjects. Blood samples were quantified for 3α,5α-tetrahydroprogesterone, 3α,5β-tetrahydroprogesterone (THP) and THDOC by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of THDOC were higher in depressed patients and decreased after fluoxetine treatment. In contrast, THP concentrations were lower in depressed patients and increased after fluoxetine treatment. Our results give further evidence for a disequilibrium of 3α-reduced neuroactive steroids in major depression, which is normalized by treatment with fluoxetine.
Anna F Dominiczak - One of the best experts on this subject based on the ideXlab platform.
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common polymorphisms at the cyp17a1 locus associate with steroid phenotypenovelty and significance support for blood pressure genome wide association study signals at this locus
Hypertension, 2016Co-Authors: Louise A Diver, Scott M Mackenzie, R Fraser, Frances Mcmanus, Marie E Freel, Samantha Alvarezmadrazo, John D Mcclure, Elaine C Friel, Neil A Hanley, Anna F DominiczakAbstract:Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of Tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects.
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common polymorphisms at the cyp17a1 locus associate with steroid phenotypenovelty and significance
Hypertension, 2016Co-Authors: Louise A Diver, Scott M Mackenzie, R Fraser, Frances Mcmanus, Marie E Freel, Samantha Alvarezmadrazo, John D Mcclure, Elaine C Friel, Neil A Hanley, Anna F DominiczakAbstract:Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of Tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects. # Novelty and Significance {#article-title-30}
Augusto Pasini - One of the best experts on this subject based on the ideXlab platform.
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Changes in CCK-4 induced panic after treatment with the GABA-reuptake inhibitor tiagabine are associated with an increase in 3α,5α-Tetrahydrodeoxycorticosterone concentrations
Psychoneuroendocrinology, 2009Co-Authors: P Zwanzger, D Eser, T C Baghai, F Padberg, Elena Romeo, Flavia Di Michele, Augusto Pasini, R RupprechtAbstract:Summary There is evidence that gamma-amino-butyric acid type A (GABA A )-receptor modulating neuroactive steroids play a role in the pathophysiology of panic disorder. Antidepressant treatment has been suggested to stabilize the concentrations of neuroactive steroids. In this pilot study we investigated neuroactive steroid concentrations during GABAergic treatment, which might represent an alternative anxiolytic pharmacotherapeutic strategy. Neuroactive steroid concentrations were determined in 10 healthy subjects treated with tiagabine. To evaluate the anxiolytic effects of tiagabine a cholecystokinine-tetrapeptide (CCK-4) challenge was performed before and after treatment. Treatment with tiagabine led to a significant increase in 3α,5α-Tetrahydrodeoxycorticosterone (3α,5α-THDOC) from 0.49 to 1.42 nmol/l ( Z = −2.80, p = .005), which was significantly correlated with a decrease of panic symptoms in the CCK-4 challenge. Thus, it might be hypothesized that the anxiolytic effects of GABAergic treatment might in part be mediated by their influence on 3α,5α-THDOC concentrations.
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mirtazapine does not influence Tetrahydrodeoxycorticosterone levels in depressed patients
World Journal of Biological Psychiatry, 2007Co-Authors: Cornelius Schule, T C Baghai, Elena Romeo, Flavia Di Michele, Augusto Pasini, Daniela Eser, Rainer RupprechtAbstract:Background. Among the neuroactive steroids, 3a,5a-Tetrahydrodeoxycorticosterone (3a,5a-THDOC) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA) system. The antidepressant mirtazapine has been shown to attenuate HPA axis activity and to increase the concentrations of 3a-reduced metabolites of progesterone in depressed patients. In the present study, the impact of mirtazapine on 3a,5aTHDOC levels was investigated in relation to clinical response in depressed patients. Method. A total of 23 drug-free inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 08:00 h and were quantified for 3a,5a-THDOC levels. Results. 3a,5aTHDOC levels were not correlated with demographic and clinical parameters such as age and severity of depression. Moreover, 5-week treatment with mirtazapine did not influence the 3a,5a-THDOC in the depressed patients, neither in responders nor in non-responders. Conclusion. Putative increasing effects of mirtazapine on 3a-reduced neuroactive steroids such as 3a,5a-THDOC which may be mediated via an impact on the neurosteroidogenic enzyme 3a-hydroxysteroid dehydrogenase seem to be counterbalanced by the mirtazapine-induced inhibition of ACTH secretion which directly influences the 3a,5a-THDOC release of the adrenal cortex.
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panic induction with cholecystokinin tetrapeptide cck 4 increases plasma concentrations of the neuroactive steroid 3 alpha 5 alpha Tetrahydrodeoxycorticosterone 3 alpha 5 alpha thdoc in healthy volunteers
Neuropsychopharmacology, 2005Co-Authors: Daniela Eser, P Zwanzger, T C Baghai, Flavia Di Michele, Augusto Pasini, Cornelius Schule, Rainer Rupprecht, Elena RomeoAbstract:3α-reduced neuroactive steroids such as 3α, 5α-tetrahydroprogesterone (3α, 5α-THP) and 3α, 5α-Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) are potent positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3α, 5α-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3α, 5α-THDOC concentrations during experimental panic induction. Therefore, we quantified 3α, 5α-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3α, 5α-THDOC, ACTH and cortisol concentrations. This increase in 3α, 5α-THDOC might be a consequence of hypothalamic–pituitary–adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.
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fluoxetine decreases concentrations of 3α 5α Tetrahydrodeoxycorticosterone thdoc in major depression
Journal of Psychiatric Research, 2000Co-Authors: Andreas Strohle, Elena Romeo, Augusto Pasini, B Hermann, Gianfranco Spalletta, F Di Michele, Florian Holsboer, Rainer RupprechtAbstract:There is evidence for a differential alteration in the concentrations of 3α-reduced neuroactive steroids in major depression. Because it has been suggested that fluoxetine may shift the activity of the 3α-hydroxysteroid oxidoreductase towards the reductive direction, treatment of major depression may be accompanied by a further increase in plasma 3α,5α-Tetrahydrodeoxycorticosterone (THDOC) concentration. We studied eight male depressed patients before and after treatment with fluoxetine and compared them to healthy age-matched control subjects. Blood samples were quantified for 3α,5α-tetrahydroprogesterone, 3α,5β-tetrahydroprogesterone (THP) and THDOC by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of THDOC were higher in depressed patients and decreased after fluoxetine treatment. In contrast, THP concentrations were lower in depressed patients and increased after fluoxetine treatment. Our results give further evidence for a disequilibrium of 3α-reduced neuroactive steroids in major depression, which is normalized by treatment with fluoxetine.
Louise A Diver - One of the best experts on this subject based on the ideXlab platform.
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common polymorphisms at the cyp17a1 locus associate with steroid phenotypenovelty and significance support for blood pressure genome wide association study signals at this locus
Hypertension, 2016Co-Authors: Louise A Diver, Scott M Mackenzie, R Fraser, Frances Mcmanus, Marie E Freel, Samantha Alvarezmadrazo, John D Mcclure, Elaine C Friel, Neil A Hanley, Anna F DominiczakAbstract:Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of Tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects.
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common polymorphisms at the cyp17a1 locus associate with steroid phenotypenovelty and significance
Hypertension, 2016Co-Authors: Louise A Diver, Scott M Mackenzie, R Fraser, Frances Mcmanus, Marie E Freel, Samantha Alvarezmadrazo, John D Mcclure, Elaine C Friel, Neil A Hanley, Anna F DominiczakAbstract:Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of Tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects. # Novelty and Significance {#article-title-30}
P Zwanzger - One of the best experts on this subject based on the ideXlab platform.
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Changes in CCK-4 induced panic after treatment with the GABA-reuptake inhibitor tiagabine are associated with an increase in 3α,5α-Tetrahydrodeoxycorticosterone concentrations
Psychoneuroendocrinology, 2009Co-Authors: P Zwanzger, D Eser, T C Baghai, F Padberg, Elena Romeo, Flavia Di Michele, Augusto Pasini, R RupprechtAbstract:Summary There is evidence that gamma-amino-butyric acid type A (GABA A )-receptor modulating neuroactive steroids play a role in the pathophysiology of panic disorder. Antidepressant treatment has been suggested to stabilize the concentrations of neuroactive steroids. In this pilot study we investigated neuroactive steroid concentrations during GABAergic treatment, which might represent an alternative anxiolytic pharmacotherapeutic strategy. Neuroactive steroid concentrations were determined in 10 healthy subjects treated with tiagabine. To evaluate the anxiolytic effects of tiagabine a cholecystokinine-tetrapeptide (CCK-4) challenge was performed before and after treatment. Treatment with tiagabine led to a significant increase in 3α,5α-Tetrahydrodeoxycorticosterone (3α,5α-THDOC) from 0.49 to 1.42 nmol/l ( Z = −2.80, p = .005), which was significantly correlated with a decrease of panic symptoms in the CCK-4 challenge. Thus, it might be hypothesized that the anxiolytic effects of GABAergic treatment might in part be mediated by their influence on 3α,5α-THDOC concentrations.
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panic induction with cholecystokinin tetrapeptide cck 4 increases plasma concentrations of the neuroactive steroid 3 alpha 5 alpha Tetrahydrodeoxycorticosterone 3 alpha 5 alpha thdoc in healthy volunteers
Neuropsychopharmacology, 2005Co-Authors: Daniela Eser, P Zwanzger, T C Baghai, Flavia Di Michele, Augusto Pasini, Cornelius Schule, Rainer Rupprecht, Elena RomeoAbstract:3α-reduced neuroactive steroids such as 3α, 5α-tetrahydroprogesterone (3α, 5α-THP) and 3α, 5α-Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) are potent positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3α, 5α-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3α, 5α-THDOC concentrations during experimental panic induction. Therefore, we quantified 3α, 5α-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3α, 5α-THDOC, ACTH and cortisol concentrations. This increase in 3α, 5α-THDOC might be a consequence of hypothalamic–pituitary–adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.
