Glucocorticoid administration increases receptor-mediated and forskolin-stimulated cyclic AMP accumulation in rat brain cerebral cortical slices

doi:10.1016/0006-8993(89)91404-2

Brain Research

Volume 477, Issues 1–2, 16 January 1989, Pages 166-171

https://doi.org/10.1016/0006-8993(89)91404-2 Get rights and content

Abstract

Experiments were undertaken to examine the influence of dexamethasone administration on adrenergic receptor-mediated cAMP accumulation in rat brain cerebral cortical slices. While the initial response to continuous treatment with dexamethasone or ACTH was a decrease in the α-adrenergic receptor-mediated augmentation of isoproterenol-stimulated cAMP production, more prolonged administration of these substances also increased β-adrenergic receptor-stimulated cAMP accumulation. Dose-response studies revealed a dose-dependent increase in β-adrenergic receptor-stimulated cAMP production. Prolonged administration of either dexamethasone or ACTH also increased 2-chloradenosine-, vasoactive intestinal peptide (VIP)-, and forskolin-stimulated cAMP production in the brain slice. These results, together with previous findings, suggest that glucocorticoids have at least two effects on the brain neurotransmitter receptor-coupled cAMP generating system which may be important for maintaining homeostasis during times of stress.

References (20)

R.S. Duman et al.
A procedure for measuring α₂-adrenergic receptor mediated inhibition of cyclic AMP accumulation in rat brain slices
Brain Research
(1986)
Y. Salomon et al.
A highly sensitive adenylate cyclase assay
Anal. Biochem.
(1974)
M.A. Brostrom et al.
Adenosine 3′,5′-monophosphate in glial tumor cells treated with glucocorticoids
Mol. Pharmacol.
(1974)
J.W. Daly et al.
Fluoronorepinephrine: specific agonists for the activation of alpha and beta adrenergic sensitive cyclic AMP-generating systems in brain slices
J. Pharmacol. Exp. Ther.
(1980)
R.S. Duman et al.
Effect of imipramine and adrenocorticotropin administration on the rat brain norepinephrine-coupled cyclic nucleotide system: alterations in alpha and beta adrenergic components
J. Pharmacol. Exp. Ther.
(1985)
R.S. Duman et al.
An examination of the involvement of phospholipase A₂ and C in the α-adrenergic and γ-aminobutyric acid receptor modulation of cyclic AMP accumulation in rat brain slices
J. Neurochem.
(1986)
R.S. Duman et al.
On the relationship between hormones depression and neurotransmitter receptor responses to antidepressants
C. Forray et al.
Glucocorticoids potentiate the prostaglandin E₁-mediated cyclic AMP formation by a cultured murine neuroblastoma clone
J. Neurochem.
(1985)
S.J. Foster et al.
Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E
A. Frazer et al.
Influence of acute and chronic treatment with desmethylimipramine on catecholamine effects in the rat
J. Pharmacol. Exp. Ther.
(1978)

There are more references available in the full text version of this article.

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Citation Excerpt :
These studies suggest a bimodal effect of glucocorticoids, in that an initial response to continuous treatment with dexamethasone or ACTH is a decrease in α-adrenergic receptor- stimulated cAMP production but more prolonged administration of these substances also increases β-adrenergic-stimulated cAMP formation. Furthermore, dexamethasone and corticosterone both enhance the sensitivity of the rat brain cAMP-generating system to forskolin (Duman et al., 1989; Czyrak, 1996). Besides the effects of stress or of glucocorticoid administration on cAMP formation, alterations in the expression of adenylyl cyclase have also been reported.
Exposure of stress precipitates a coordinated series of responses which may lead to changes in brain functions. Most of the changes in brain function are mediated by stress-induced activation of neurotransmitter systems in the brain, which include neurotransmitter receptors and these receptors-mediated signal transduction pathways. The signal transduction pathways are ultimately responsible for stress-induced changes in neuronal functions. Some of these changes are beneficial, however, depending upon the nature and duration of stressful stimuli, the changes in neuronal functions may be harmful, which may lead to many disorders. In the present chapter, we describe comprehensively the effects of stress on neurotransmitter receptors and various molecules of signal transduction pathways in brain
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It is well established that glucocorticoid hormones, secreted by the adrenal cortex after a stressful event, influence cognitive performance. This article reviews recent findings from this laboratory on the acute effects of glucocorticoids in rats on specific memory phases, i.e., memory consolidation and memory retrieval. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors (GRs) enhances memory consolidation in a dose-dependent manner. Glucocorticoid influences on memory consolidation depend on noradrenergic activation of the basolateral complex of the amygdala (BLA) and interactions of the BLA with other brain regions. By contrast, memory retrieval processes are usually impaired with high circulating levels of glucocorticoids or following infusions of GR agonists into the hippocampus. Although the BLA does not appear to be a site of glucocorticoid action in influencing memory retrieval, an intact BLA is required for enabling glucocorticoid effects on memory retrieval. The BLA appears to be a key structure in a memory-modulatory system that regulates, in concert with other brain regions, stress and glucocorticoid effects on both memory consolidation and memory retrieval.
Functional effects of corticosterone on 5-HT<inf>1A</inf> and 5-HT<inf>1B</inf> receptor activity in rat brain: In vivo microdialysis studies
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Glucocorticoid hormones are known to be elevated in depression, and to interact with serotonin 5-HT_1A receptors at both the presynaptic and postsynaptic levels. Since one of the presumed mechanisms of action of antidepressant drugs is induction of changes in sensitivity of 5-HT_1A and also 5-HT_1B receptors, the effects of repeated administration of corticosterone (50 mg/kg s.c. b.i.d. for 10 days) on activities of these receptors were determined using in vivo microdialysis in freely moving rats. Presynaptic 5-HT_1A receptor activity, as measured by the effect of a challenge dose (0.2 mg/kg s.c.) of the 5-HT_1A agonist 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) to reduce 5-HT levels in the hypothalamus, was not affected by corticosterone administration. Presynaptic 5-HT_1B receptor activity, as measured by the effect of the 5-HT_1B receptor antagonist (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazole-3-yl)[1,1′-biphenyl]-carboxamide (GR 127935) (5 mg/kg s.c.) to increase 5-HT levels, was increased in hypothalamus but not hippocampus of corticosterone-treated rats. Postsynaptic 5-HT_1A receptor activity, as measured by the effect of 8-OH-DPAT to increase cyclic AMP levels in the hippocampus, was not affected by corticosterone administration. The decrease in presynaptic 5-HT_1B receptor activity after chronic administration of antidepressant drugs complements the increases in 5-HT_1B receptor number observed in animal models of depression.
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This paper summarizes recent findings on the amygdala’s role in mediating acute effects of glucocorticoids on memory consolidation in rats. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors (GRs or type II) enhances memory consolidation in a dose-dependent inverted-U fashion. Selective lesions of the basolateral nucleus of the amygdala (BLA) or infusions of β-adrenoceptor antagonists into the BLA block the memory-modulatory effects of systemic injections of glucocorticoids. Additionally, posttraining infusions of a specific GR agonist administered directly into the BLA enhance memory consolidation, whereas those of a GR antagonist impair. These findings indicate that glucocorticoid effects on memory consolidation are mediated, in part, by an activation of GRs in the BLA and that the effects require β-adrenergic activity in the BLA. Other findings indicate that the BLA interacts with the hippocampus in mediating glucocorticoid-induced modulatory influences on memory consolidation. Lesions of the BLA or inactivation of β-adrenoceptors within the BLA also block the memory-modulatory effects of intra-hippocampal administration of a GR agonist or antagonist. These findings are in agreement with the general hypothesis that the BLA integrates hormonal and neuromodulatory influences on memory consolidation. However, the BLA is not a permanent locus of storage for this information, but modulates consolidation processes for explicit/associative memories in other brain regions, including the hippocampus.
Effects of acute and chronic administration of high-dose corticosterone and dexamethasone on regional brain dopamine and serotonin metabolism in rats
1996, Progress in Neuro-Psychopharmacology and Biological Psychiatry
- 1.
  1. The effects of acute and chronic treatment with high-dose corticosterone (50 mg/kg) and dexamethasone (0.7 mg/kg) on monoamines and their metabolites levels in four regions of the rat brain were investigated.
- 2.
  2. Acute corticosterone and dexamethasone treatment decreased serotonin (5-HT) levels, but did not alter dopaMine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5-HIAA) levels in any of the brain regions.
- 3.
  3. Chronic corticosterone treatment significantly increased the HVA and 5-HIAA levels only in the medial prefrontal cortex, while chronic dexamethasone treatment did not alter. Chronic corticosterone and dexamethasone treatment did not change DA, DOPAC or 5-HT levels in any of the brain regions.
- 4.
  4. These findings suggest that chronic treatment with high-dose corticosterone activates the dopaminergic and serotonergic neurotransmission in the medial prefrontal cortex.

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^∗: Present address: Nova Pharmaceutical Corporation, 6200 Freeport Centre, Baltimore, MD 21224, U.S.A.

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Research reportGlucocorticoid administration increases receptor-mediated and forskolin-stimulated cyclic AMP accumulation in rat brain cerebral cortical slices

Abstract

Brain Research

Anal. Biochem.

Adenosine 3′,5′-monophosphate in glial tumor cells treated with glucocorticoids

Mol. Pharmacol.

Fluoronorepinephrine: specific agonists for the activation of alpha and beta adrenergic sensitive cyclic AMP-generating systems in brain slices

J. Pharmacol. Exp. Ther.

Effect of imipramine and adrenocorticotropin administration on the rat brain norepinephrine-coupled cyclic nucleotide system: alterations in alpha and beta adrenergic components

J. Pharmacol. Exp. Ther.

An examination of the involvement of phospholipase A2 and C in the α-adrenergic and γ-aminobutyric acid receptor modulation of cyclic AMP accumulation in rat brain slices

J. Neurochem.

On the relationship between hormones depression and neurotransmitter receptor responses to antidepressants

Glucocorticoids potentiate the prostaglandin E1-mediated cyclic AMP formation by a cultured murine neuroblastoma clone

J. Neurochem.

Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E

Influence of acute and chronic treatment with desmethylimipramine on catecholamine effects in the rat

J. Pharmacol. Exp. Ther.

Research report
Glucocorticoid administration increases receptor-mediated and forskolin-stimulated cyclic AMP accumulation in rat brain cerebral cortical slices

An examination of the involvement of phospholipase A₂ and C in the α-adrenergic and γ-aminobutyric acid receptor modulation of cyclic AMP accumulation in rat brain slices

Glucocorticoids potentiate the prostaglandin E₁-mediated cyclic AMP formation by a cultured murine neuroblastoma clone