Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.

Brady, Linda S.; Whitfield, Harvey J.; Fox, Robert J.; Gold, Philip W.; Herkenham, Miles

doi:10.1172/jci115086

Cited by 326 publications

(165 citation statements)

References 27 publications

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“…Comparable to imipramine, the SJW extract and hypericin reduced plasma ACTH and corticosterone levels after 2 weeks of daily treatment. In line with previous findings (Brady et al, 1991;Nestler et al, 1990), we found that long-term treatment with imipramine significantly decreased TH mRNA levels in the locus coeruleus, whereas SJW extract and hypericin had no effect on TH message levels. Furthermore, long-term treatment with all three agents significantly decreased 5-HT 1A receptor mRNA expression in CA1 of the hippocampus.…”

Section: Introductionsupporting

confidence: 92%

“…In an animal study designed to examine the association between long-term antidepressant administration and the possibly delayed alteration in HPA axis activity, CRH mRNA levels in the hypothalamic paraventricular nucleus (PVN) of rats were shown to be decreased following longterm (8 weeks) but not short-term (2 weeks) treatment with imipramine, the prototypic tricyclic antidepressant (Brady et al, 1991). The same results were found with several other antidepressant drugs selected for their distinctly different primary pharmacological actions (Brady et al, 1992).…”

Section: Introductionmentioning

confidence: 68%

“…The in situ hybridization histochemistry procedures were performed as described previously for ribonucleotide (cRNA) probes (Brady et al, 1991). First, tissue sections were processed by fixation with 4% formaldehyde solution, acetylation with 0.25% acetic anhydride in 0.1 M triethanolamine-HCl, pH 8.0 solution, dehydration with ethanol, and delipidation with chloroform.…”

Section: In Situ Hybridization Histochemistrymentioning

confidence: 99%

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Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

Butterweck

Winterhoff²,

Herkenham

2003

Neuropsychopharmacol

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We previously showed that a methanolic extract of St John's wort (SJW) (Hypericum) and hypericin, one of its active constituents, both have delayed regulation of genes that are involved in the control of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperforin, another constituent of SJW, is active in vitro and has been proposed to be the active constituent for therapeutic efficacy in depression. We therefore examined if hyperforin has delayed effects on HPA axis control centers similar to those of Hypericum and hypericin. We used in situ hybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) oral administration of two hyperforin preparations, fluoxetine (positive control), and haloperidol (negative control) on the expression of genes involved in the regulation of the HPA axis. Fluoxetine (10 mg/kg) given daily for 8 weeks, but not 2 weeks, significantly decreased levels of corticotropinreleasing hormone (CRH) mRNA by 22% in the paraventricular nucleus (PVN) of the hypothalamus and tyrosine hydroxylase (TH) mRNA by 23% in the locus coeruleus. Fluoxetine increased levels of mineralocorticoid (MR) (17%), glucocorticoid (GR) (18%), and 5-HT 1A receptor (21%) mRNAs in the hippocampus at 8, but not 2, weeks. Comparable to haloperidol (1 mg/kg), neither the hyperforinrich CO 2 extract (27 mg/kg) nor hyperforin-trimethoxybenzoate (8 mg/kg) altered mRNA levels in brain structures relevant for HPA axis control at either time point. These data suggest that hyperforin and hyperforin derivatives are not involved in the regulation of genes that control HPA axis function.

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Section: Introductionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 68%

Section: In Situ Hybridization Histochemistrymentioning

confidence: 99%

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Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

Butterweck

Winterhoff²,

Herkenham

2003

Neuropsychopharmacol

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“…Another system that is markedly altered following chronic antidepressant treatment is the HPA axis. For example, following long (8 weeks), but not short (2 weeks) treatment with either fluoxetine or imipramine, CRH mRNA was decreased by 30-48% in the hypothalamic PVN (Brady et al 1991(Brady et al , 1992. Moreover, chronic treatment with fluoxetine, as well as other antidepressants, significantly elevated the levels of glucocorticoid receptors in the hippocampus (Brady et al 1991(Brady et al , 1992, which normally mediate the negative feedback response to stress-induced activation of the HPA axis (Sapolsky et al 1984).…”

Section: Discussionmentioning

confidence: 99%

“…For example, following long (8 weeks), but not short (2 weeks) treatment with either fluoxetine or imipramine, CRH mRNA was decreased by 30-48% in the hypothalamic PVN (Brady et al 1991(Brady et al , 1992. Moreover, chronic treatment with fluoxetine, as well as other antidepressants, significantly elevated the levels of glucocorticoid receptors in the hippocampus (Brady et al 1991(Brady et al , 1992, which normally mediate the negative feedback response to stress-induced activation of the HPA axis (Sapolsky et al 1984). Finally, our results are in agreement with previous studies in experimental animals (Reul et al 1993) and in healthy humans (Michelson et al 1997), which reported that chronic treatment with antidepressants markedly attenuated the pituitary-adrenal response to stressful or pharmacological challenges.…”

Section: Discussionmentioning

confidence: 99%

Effects of Antidepressant Drugs on the Behavioral and Physiological Responses to Lipopolysaccharide (LPS) in Rodents

Yirmiya

Pollak

Barak

et al. 2001

Neuropsychopharmacology

203

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Antidepressants produce various immunomodulatory effects, as well as an attenuation of the behavioral responses to immune challenges, such as lipopolysaccharide (LPS). To explore further the effects of antidepressants on neuroimmune interactions, rats were treated daily with either fluoxetine (Prozac) or saline for 5 weeks, and various behavioral, neuroendocrine, and immune functions were measured following administration of either LPS or saline. Chronic fluoxetine treatment significantly attenuated the anorexia and body weight loss, as well as the depletion of CRH-41 from the median eminence and the elevation in serum corticosterone levels induced by LPS. Chronic treatment with imipramine also attenuated LPS-induced adrenocortical activation. In rats and in mice, which normally display a biphasic body temperature response to LPS (initial hypothermia followed by hyperthermia), chronic treatment with fluoxetine completely abolished the hypothermic response and facilitated and strengthened the hyperthermic response. The effects of antidepressants on the responsiveness to LPS are probably not mediated by their effects on peripheral proinflammatory cytokine production, because LPS-induced expression of TNFSeveral lines of evidence indicate that antidepressants produce various immunomodulatory effects. In depressed patients, the effects of antidepressants are variable and seem to be related to the immune status of the patients at the initiation of the treatment. When depression was associated with immune activation, antidepressants reduced immune function and cytokine secretion. For example, the increased plasma levels of IL-6 during acute depression were normalized by 8-week treatment with fluoxetine (Sluzewska et al. 1995), the increased monocyte counts in depressed patients were reduced following 6-weeks treatment with tricyclic antidepressants (TCAs) (Seidel et al. 1996), and the increased numbers of leukocytes and neutrophils were also reduced by antidepressant treatment (Maes et al. 24 , NO . 5 1997). On the other hand, when immune functions were found to be normal, antidepressants had no immunological effects; for example, chronic moclobemide treatment had no effect on monocytes functions, TNF ␣ production or IFN ␥ levels (Landmann et al. 1997). Moreover, in a study of depressed patients who exhibited immune suppression before treatment, the TCA clomipramine increased the production of IL-1 ␤ , IL-2, and IL-3 (Weizman et al. 1994).In experimental animals, TCAs as well as selective serotonin reuptake inhibitors (SSRIs) produce mainly immune suppression and anti-inflammatory effects. For example, antidepressant treatment in vivo inhibited the increased acute phase response in olfactory bulbectomized rats, a useful animal model of depression (Song and Leonard 1994), reduced the production of interleukin-1 (IL-1) and IL-2 in a chronic mild stress model of depression (Kubera et al. 1996), inhibited immune activation in rats with experimental allergic neuritis (Zhu et al. 1994), and produced anti-inflammatory ...

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Sympathetic Nervous System Activity in Major Depression

Veith

Lewis²,

Linares

et al. 1994

Arch Gen Psychiatry

385

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Sympathetic nervous system activity is elevated in major depression and is suppressed by short-term desipramine administration. The demonstration of SNS reactivation occurring with prolonged desipramine treatment is compatible with the theory that long-term treatment desensitizes CNS alpha 2-adrenergic receptors and emphasizes the value of examining the temporal course of responses to pharmacological challenges of neuroendocrine systems. Previously reported elevations of plasma NE during prolonged administration of tricyclic antidepressants are probably the result of a reduction in plasma NE clearance, not an increase in SNS activity.

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Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.

Cited by 326 publications

References 27 publications

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

Effects of Antidepressant Drugs on the Behavioral and Physiological Responses to Lipopolysaccharide (LPS) in Rodents

Sympathetic Nervous System Activity in Major Depression

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