Benzodiazepine receptors in rat cerebral cortex and hippocampus undergo rapid and reversible changes after acute stress

Medina, Jorge H.; Novas, M.L.; Wolfman, Claudia; Stein, Miguelina Levi de; Robertis, E. De

doi:10.1016/0306-4522(83)90298-1

Cited by 115 publications

(26 citation statements)

References 17 publications

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“…Stimulation of central benzodiazepine receptors increases the affinity of GABA for its binding site through positive allosteric effects, potentiating GABAergic transmission (Zavala, 1997). Isolation (present results) or exposure to inescapable stressors such as foot shock or forced swimming (Lippa et al, 1978;Weizman et al, 1989;Medina et al, 1983) decreased benzodiazepine receptor binding in the frontal cortex. In turn, decreased benzodiazepine binding decreases GABAergic transmission, and this leads to stress-induced anxiety (Nutt and Malizia, 2001).…”

Section: Discussionsupporting

confidence: 48%

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

Saavedra

Armando

Bregonzio

et al. 2005

Neuropsychopharmacol

101

100

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Long-term pretreatment with an angiotensin II AT 1 antagonist blocks angiotensin II effects in brain and peripheral organs and abolishes the sympathoadrenal and hypothalamic-pituitary-adrenal responses to isolation stress. We determined whether AT 1 receptors were also important for the stress response of higher regulatory centers. We studied angiotensin II and corticotropin-releasing factor (CRF) receptors and benzodiazepine binding sites in brains of Wistar Hannover rats. Animals were pretreated for 13 days with vehicle or a central and peripheral AT 1 antagonist (candesartan, 0.5 mg/kg/day) via osmotic minipumps followed by 24 h of isolation in metabolic cages, or kept grouped throughout the study (grouped controls). In another study, we determined the influence of a similar treatment with candesartan on performance in an elevated plus-maze. AT 1 receptor blockade prevented the isolation-induced increase in brain AT 1 receptors and decrease in AT 2 binding in the locus coeruleus. AT 1 receptor antagonism also prevented the increase in tyrosine hydroxylase mRNA in the locus coeruleus. Pretreatment with the AT 1 receptor antagonist completely prevented the decrease in cortical CRF 1 receptor and benzodiazepine binding produced by isolation stress. In addition, pretreatment with candesartan increased the time spent in and the number of entries to open arms of the elevated plus-maze, measure of decreased anxiety. Our results implicate a modulation of upstream neurotransmission processes regulating cortical CRF 1 receptors and the GABA A complex as molecular mechanisms responsible for the anti-anxiety effect of centrally acting AT 1 receptor antagonists. We propose that AT 1 receptor antagonists can be considered as compounds with possible therapeutic anti-stress and anti-anxiety properties.

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Section: Discussionsupporting

confidence: 48%

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

Saavedra

Armando

Bregonzio

et al. 2005

Neuropsychopharmacol

101

100

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“…2,6,[36][37][38] In general, these animal models have shown decreased GABA A function and binding in the cerebral cortex and hippocampus. [3][4][5] This is the first benzodiazepine-GABA A receptor binding study in patients with PTSD that supports these preclinical data.…”

Section: Discussionmentioning

confidence: 61%

“…2 Exposure of rodents to inescapable foot shock, a model for stress-related depression characterized by deficits in learning and memory, resulted in decreased GABA A function and binding in the cerebral cortex and hippocampus. [3][4][5] Benzodiazepines, which modulate the GABA A receptor function, inhibit the startle response induced by predator stress. 6 These predator stress paradigms model aspects of hyperarousal seen in patients with PTSD.…”

Section: Introductionmentioning

confidence: 99%

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

et al. 2007

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c-Aminobutyric acid (GABA A ) receptors are thought to play an important role in modulating the central nervous system in response to stress. Animal data have shown alterations in the GABA A receptor complex by uncontrollable stressors. SPECT imaging with benzodiazepine ligands showed lower distribution volumes of the benzodiazepine-GABA A receptor in the prefrontal cortex of patients with post-traumatic stress disorder (PTSD) in one, but not in another study. The objective of the present study was to assess differences in the benzodiazepine-GABA A receptor complex in veterans with and without PTSD using [ 11 C]flumazenil and positron emission tomography (PET). Nine drug naive male Dutch veterans with deployment related PTSD and seven male Dutch veterans without PTSD were recruited, and matched for age, region and year of deployment. Each subject received a [ 11 C]flumazenil PET scan and a structural magnetic resonance imaging scan. Dynamic 3D PET scans with a total duration of 60 min were acquired, and binding in template based and manually defined regions of interest (ROI) was quantified using validated plasma input and reference tissue models. In addition, parametric binding potential images were compared on a voxel-by-voxel basis using statistical parametric mapping (SPM2). ROI analyses using both template based and manual ROIs showed significantly reduced [ 11 C]flumazenil binding in PTSD subjects throughout the cortex, hippocampus and thalamus. SPM analysis confirmed these results. The observed global reduction of [ 11 C]flumazenil binding in patients with PTSD provides circumstantial evidence for the role of the benzodiazepine-GABA A receptor in the pathophysiology of PTSD and is consistent with previous animal research and clinical psychopharmacological studies.

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“…Earlier receptor binding studies demonstrated stress effects upon GABA A receptor function following both acute and chronic stress exposure (Medina et al, 1983;Rago et al, 1989). More recently, studies utilizing a hybridization histochemical approach to the analysis of GABA A subunit mRNA expression have reported similar findings.…”

Section: Stress Regulation Of Central Nervous System (Cns) Gaba a Recmentioning

confidence: 62%

GABAA receptor subunit expression within hypophysiotropic CRH neurons: A dual hybridization histochemical study

Cullinan

2000

J. Comp. Neurol.

115

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Benzodiazepine receptors in rat cerebral cortex and hippocampus undergo rapid and reversible changes after acute stress

Cited by 115 publications

References 17 publications

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

GABAA receptor subunit expression within hypophysiotropic CRH neurons: A dual hybridization histochemical study

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