Hippocampal Mineralocorticoid, but Not Glucocorticoid, Receptors Modulate Anxiety-Like Behavior in Rats

Smythe, James W.; Murphy, D L; Timothy, Carryl; Costall, B.

doi:10.1016/s0091-3057(96)00244-4

Cited by 105 publications

(61 citation statements)

References 21 publications

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“…Our behavioral data are consistent with studies using glucocorticoid and mineralocorticoid receptor antagonists, which support a role for GCs in exploring novel environments and anxietyrelated behavior (Oitzl et al, 1994;Korte et al, 1995;Smythe et al, 1997;Bitran et al, 1998;Ströhle et al, 1998). Apoe Ϫ/Ϫ mice have been the subject of numerous behavioral investigations (for example, see Gordon et al, 1995;Masliah et al, 1997;Oitzl et al, 1997;Anderson et al, 1998;Fisher et al, 1998;Raber et al, 1998).…”

Section: Discussionsupporting

confidence: 86%

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe^−/−Mice: Possible Role in Behavioral and Metabolic Alterations

et al. 2000

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Several neurological diseases are frequently accompanied by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis regulates the secretion of glucocorticoids (GCs), which play important roles in diverse brain functions, including cognition, emotion, and feeding. Under physiological conditions, GCs are adaptive and beneficial; however, prolonged elevations in GC levels may contribute to neurodegeneration and brain dysfunction. In the current study, we demonstrate that apolipoprotein E (apoE) deficiency results in agedependent dysregulation of the HPA axis through a mechanism affecting primarily the adrenal gland. Apoe Ϫ/Ϫ mice, which develop neurodegenerative alterations as they age, had an age-dependent increase in basal adrenal corticosterone content and abnormally increased plasma corticosterone levels after restraint stress, whereas their plasma and pituitary adrenocorticotropin levels were either unchanged or lower than those in controls. HPA axis dysregulation was associated with behavioral and metabolic alterations. When anxiety levels were assessed in the elevated plus maze, Apoe Ϫ/Ϫ mice showed more anxiety than wild-type controls. Apoe Ϫ/Ϫ mice also showed reduced activity in the open field. Finally, Apoe Ϫ/Ϫ mice showed age-dependent increases in food and water intake, stomach and body weights, and decreases in brown and white adipose tissues. These results support a key role for apoE in the tonic inhibition of steroidogenesis and HPA axis activity and have important implications for the behavioral analysis of Apoe Ϫ/Ϫ mice.

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Section: Discussionsupporting

confidence: 86%

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe^−/−Mice: Possible Role in Behavioral and Metabolic Alterations

et al. 2000

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“…It has been reported that corticosteroids trigger two types of responses: a genomic and a nongenomic (de Kloet et al, 1996;Smythe et al, 1997;Yamada et al, 2003;. The first one is slow, is mediated by intracellular corticosteroid receptors, and involves protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Differential Corticosteroid Modulation of Inhibitory Synaptic Currents in the Dorsal and Ventral Hippocampus

Maggio¹,

Segal²

2009

J. Neurosci.

113

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Corticosterone has been known to mediate the effects of stress on cognitive functions associated with the hippocampus. Acting at mineralocorticosteroid receptors (MRs) and glucocorticosteroid receptors (GRs), corticosterone exerts several effects in the hippocampus and elsewhere. Assuming that there are major functional differences between the dorsal hippocampus (DH) and ventral hippocampus (VH), and that these may be regulated by local interneurons, we analyzed the action of corticosterone on inhibitory synaptic currents in patch-clamped pyramidal neurons, recorded in acute slices of DH and VH. Corticosterone, through activation of MRs, reduced the frequency of spontaneous IPSCs in VH but not in DH neurons, and markedly suppressed paired-pulse facilitation of evoked inhibitory synaptic currents. These effects were mimicked by aldosterone, an MR agonist, and were blocked by an MR antagonist. In contrast, corticosterone caused an increase in the magnitude of IPSCs in both the DH and VH via its activation of GRs. This effect was mimicked by a GR agonist, dexamethasone, which produced a slow-onset, large potentiation reaching a peak within 45-60 min after onset of perfusion, and was blocked by a GR antagonist. The amplitude of mIPSCs was markedly increased by the GR agonist, indicating a synaptic locus of effect. These results indicate that corticosterone has a dual action, which may underlie the differential functional effects of stress hormones in the DH and VH.

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“…Corticosterone has two types of responses: a genomic and a nongenomic (de Kloet et al, 1996;Smythe et al, 1997;Yamada et al, 2003;. The first one requires protein synthesis and is activated by a low-affinity GR, hence is thought to be a slow response.…”

Section: Discussionmentioning

confidence: 99%

Differential Modulation of Long-Term Depression by Acute Stress in the Rat Dorsal and Ventral Hippocampus

Maggio

Segal²

2009

Journal of Neuroscience

112

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The ventral hippocampus (VH) was recently shown to express lower-magnitude long-term potentiation (LTP) than the dorsal hippocampus (DH). An exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than controls, whereas LTP in the DH was suppressed by stress. We have now used long-term depression (LTD)-generating trains of stimulation to examine whether this differential LTP reflects a genuine difference in synaptic modifiability between the two sectors of the hippocampus. Surprisingly, slices of DH and VH express similar magnitudes of LTD. However, while prior stress enhanced LTD in the DH, it actually converted LTD to slow-onset, robust LTP in the VH. These two effects of stress on LTD were blocked by glucocorticosterone receptor (GR) and mineralocorticosterone receptor (MR) antagonists, respectively. Acute exposure of slices to a GR agonist dexamethasone facilitated LTD in slices of both DH and VH, while activation of MRs by aldosterone converted LTD to LTP in both regions. Thus, differential activation of the two species of corticosterone receptors determines the ability of the two sectors of the hippocampus to undergo plastic changes in response to LTD-inducing stimulation.

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Hippocampal Mineralocorticoid, but Not Glucocorticoid, Receptors Modulate Anxiety-Like Behavior in Rats

Cited by 105 publications

References 21 publications

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe^−/−Mice: Possible Role in Behavioral and Metabolic Alterations

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe^−/−Mice: Possible Role in Behavioral and Metabolic Alterations

Differential Corticosteroid Modulation of Inhibitory Synaptic Currents in the Dorsal and Ventral Hippocampus

Differential Modulation of Long-Term Depression by Acute Stress in the Rat Dorsal and Ventral Hippocampus

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Hippocampal Mineralocorticoid, but Not Glucocorticoid, Receptors Modulate Anxiety-Like Behavior in Rats

Cited by 105 publications

References 21 publications

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe−/−Mice: Possible Role in Behavioral and Metabolic Alterations

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe−/−Mice: Possible Role in Behavioral and Metabolic Alterations

Differential Corticosteroid Modulation of Inhibitory Synaptic Currents in the Dorsal and Ventral Hippocampus

Differential Modulation of Long-Term Depression by Acute Stress in the Rat Dorsal and Ventral Hippocampus

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Hypothalamic–Pituitary–Adrenal Dysfunction inApoe^−/−Mice: Possible Role in Behavioral and Metabolic Alterations

Hypothalamic–Pituitary–Adrenal Dysfunction inApoe^−/−Mice: Possible Role in Behavioral and Metabolic Alterations