Effects of ipsapirone on plasma cortisol and body temperature in major depression

Meltzer, Herbert Y.; Maes, Michaël

doi:10.1016/0006-3223(94)00370-i

Cited by 73 publications

(42 citation statements)

References 47 publications

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“…Another significant ipsapirone-induced difference between groups was the impairment of memory performance in controls and improvement in patients. These findings are in agreement with previous separate studies that showed a blunted cortisol response to ipsapirone in depressed patients (Lesch et al 1990;Meltzer and Maes 1995) and hyperresponsivity to m-CPP in terms of subjective mood (Charney et al 1987;Lawlor et al 1989). Our strategy, the so-called functional approach, was based on the inclusion of patients with depressed moods on the basis of symptoms rather than diagnostic categories.…”

Section: Discussionsupporting

confidence: 87%

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Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

Riedel

Klaassen

Griez

et al. 2002

Neuropsychopharmacology

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Section: Discussionsupporting

confidence: 87%

“…Ipsapirone was originally developed as an antianxiety agent but also has anti-aggressive effects in rodents (De Vry 1995). In humans, blunted responses of cortisol to ipsapirone (a partial 5-HT 1A receptor agonist) were found in patients with major depression (Lesch et al 1990;Meltzer and Maes 1995).…”

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confidence: 99%

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

Riedel

Klaassen

Griez

et al. 2002

Neuropsychopharmacology

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“…The cortisol response to the 5-HT precursor 5-hydroxytryptophan (5-HTP) was enhanced in patients with major depression compared to control subjects (Meltzer et al 1984) and further increased after subchronic treatment with fluoxetine but not with tricyclic antidepressants (Meltzer et al 1997). This discrepancy is probably due to the fact that the 5-HTP induced rise in cortisol is not mediated by 5-HT 1A receptors, since in norman human volunteers pindolol inhibited the prolactin but not the cortisol response to this agent (Meltzer and Maes 1995).We examined the effect of fluoxetine administration for four weeks to normal volunteers, on temperature, ACTH, cortisol and growth hormone responses to ipsapirone challenge. Based on previous findings, we hypothesized that both the temperature and hormone responses would be blunted by fluoxetine.…”

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confidence: 99%

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Lerer¹,

Gelfin²,

Gorfine

et al. 1999

Neuropsychopharmacology

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Serotonergic receptors of the 5-HT 1A subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HTThere is considerable interest in the role of serotonergic (5-HT) receptors of the 5-HT 1A subtype in the therapeutic action of antidepressant drugs. 5-HT 1A receptors are located presynaptically on serotonergic cell bodies in the raphe nuclei where they serve as autoreceptors which inhibit cell firing and reduce 5-HT release by a negative feedback mechanism, and post-synaptically in the hippocampus, cortex and other brain areas, including the hypothalamus. Based on electrophysiological studies in rats, De Montigny and colleagues Mongeau et al. 1997) proposed that each major class of antidepressants increases 5-HT neurotransmission by a distinct mechanism involving either From the Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center (BL, YG, MEN) and the Laboratory of Applied Statistics, Hebrew University (MG), Jerusalem, Israel; the Endocrine Laboratory, Department of Medicine (BA) and Department of Psychiatry (KPL), University of Wuerzburg, Wuerzburg, Germany.Address correspondence to: Prof. Bernard Lerer, Biological Psychiatry Laboratory, Dept. of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel.Received May 15, 1998; accepted August 25, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 Ipsapirone Challenge in Normal Subjects on Fluoxetine 629pre-or post-synaptic 5-HT 1A receptors. The selective serotonin re-uptake inhibitors (SSRIs), which raise 5-HT synaptic levels when given acutely, were proposed to increase 5-HT transmission on repeated administration by inducing desensitization of somatodendritic 5-HT 1A autoreceptors in the raphe nuclei and nerve terminal 5-HT 1B autoreceptors, which also mediate feedback inhibition of 5-HT release. These effects would lead to a slow increase in 5-HT levels which corresponds to the delayed clinical effect of the drugs. Evidence for subsensitivity of somatodendritic 5-HT 1A autoreceptors after chronic administration of SSRIs has been provided by microdialysis experiments in which 5-HT levels are measured in vivo in response to a challenge dose of the 5-HT 1A receptor agonist, 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) (Rutter et al. 1994, Kreiss andLucki 1995;Invernizzi et al. 1994). However, other studies using SSRIs (Hjorth and Auerbach 1994; Bosker et al. 1995a,b;Invernizzi et al. 1995Invernizzi et al. , 1996 or clomipramine (Gur et al. 1999) failed to show any change in 5-HT 1A autoreceptor subsensitivity by this method. An increase in basal 5-HT levels after chronic SSRI administration, taken to be due to pre-synaptic 5-HT 1A and 5-HT 1B receptor desensitization, has been observed in cortex (Bel and Artigas 1993), hippocampus (Auerbach and Hjorth 1995) diencephalon (Rutter et al. 1994) an...

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“…Pharmacological manipulations of 5-HT, including ipsapirone challenge, are known to induce a cortisol response through the hypothalamic-pituitary-adrenal (HPA) axis. This is especially pertinent, given suggestions that depressed individuals show a blunted cortisol response to ipsapirone challenge (Meltzer and Maes, 1995; …”

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confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT 1A and 5-HT 3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT 1A agonists ameliorate memory deficits in depression. INTRODUCTIONHypofunction of the 5-hydroxytryptamine (5-HT) system has emerged as a leading candidate cause for depression (Naughton et al, 2000;Middlemiss et al, 2002). At the same time, several lines of evidence point to a role for 5-HT in memory (Buhot et al, 2000). Most prominently, depletion of tryptophan (TRP), a precursor of 5-HT, is associated with lower performance on episodic memory retention tests in humans (Riedel et al, 1999). This mirrors findings in depression, which is accompanied by moderate to severe memory deficits (Johnson and Magaro, 1987;Schaub et al, 2003). However, manipulations that increase 5-HT concentration or 5-HT receptor activation also lower memory performance, as indicated by receptor agonist studies in both humans (Riedel et al, 2002) and animals (Altman and Normile, 1988). Up to now, it is not known why both increased and decreased 5-HT activation have adverse effects on memory.5-HT binds to a large and disparate family of CNS receptors, which have effects that are sometimes opposite. Thus, many effects of different receptors seem to cancel each other out. In a review (see Supplementary Information on internet), we identify two robust effects of 5-HT in the hippocampus. First, 5-HT exerts a hyperpolarizing influence on principal cells; directly, via 5-HT 1A receptors, and indirectly, via facilitation of GABA release from local interneurons through 5-HT 3 receptors (Burnet et al, 1995;Piguet and Galvan, 1994). Activation of 5-HT 2A and 5-HT 2C receptors has been suggested to induce depolarization in principal cells (Piguet and Galvan, 1994;Barnes and Sharp, 1999), but these effects appear to be dominated by the depolarizing effects of 5-HT, as bath application of 5-HT will hyperpolarize principal cells in slice preparations of the dentate gyrus (Piguet and Galvan, 1994). In addition, through 5-HT 2C , 5-HT 4 , and 5-HT 7 receptors, afterhyperpolarizing (AHP) currents are downregulated, leading to reduced adaptation in principal cells (Torres et al, 1996;Bac...

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Effects of ipsapirone on plasma cortisol and body temperature in major depression

Cited by 73 publications

References 47 publications

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Effects of 5-HT on Memory and the Hippocampus: Model and Data

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