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

Lerer, Bernard; Gelfin, Yevgenia; Gorfine, Malka; Allolio, Bruno; Lesch, Klaus‐Peter; Newman, Morris

doi:10.1016/s0893-133x(98)00106-7

Cited by 79 publications

(48 citation statements)

References 61 publications

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“…Healthy individuals treated with fluoxetine had blunted hormonal responses to 5-HT 1A challenge, indicative of downregulation of both pre-and postsynaptic 5-HT 1A receptors. 45 Furthermore, 3-week treatment of healthy volunteers with paroxetine led to desensitized 5-HT 2 receptors as evidenced by a blunted prolactin response. 46 Since many participants in the Moreno et al study were on SSRIs (and some may have been on SSRIs in the past), one could speculate that SSRIs may affect the function of 5-HT neurotransmission particularly in l/l genotype individuals.…”

Section: Acute Tryptophan Depletionmentioning

confidence: 99%

Monoamine depletion in psychiatric and healthy populations: review

2003

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A number of techniques temporarily lower the functioning of monoamines: acute tryptophan depletion (ATD), alpha-methyl-para-tyrosine (AMPT) and acute phenylalanine/tyrosine depletion (APTD). This paper reviews the results of monoamine depletion studies in humans for the period 1966 until December 2002. The evidence suggests that all three interventions are specific, in terms of their short-term effects on one or two neurotransmitter systems, rather than on brain protein metabolism in general. The AMPT procedure is somewhat less specific, affecting both the dopamine and norepinephrine systems. The behavioral effects of ATD and AMPT are remarkably similar. Neither procedure has an immediate effect on the symptoms of depressed patients; however, both induce transient depressive symptoms in some remitted depressed patients. The magnitude of the effects, response rate and quality of response are also comparable. APTD has not been studied in recovered major depressive patients. Despite the similarities, the effects are distinctive in that ATD affects a subgroup of recently remitted patients treated with serotonergic medications, whereas AMPT affects recently remitted patients treated with noradrenergic medications. The evidence also suggests that ATD and APTD affect different cognitive functions, in particular different memory systems. Few studies investigated cognitive effects of the procedures in patients. Patients who are in remission for longer may also be vulnerable to ATD and AMPT, but the relationship with prior treatment is much weaker. For these patients, individual vulnerability markers are the more important determinants of depressive response, making these techniques potentially useful models of vulnerability to depression. Molecular Psychiatry (2003) 8, 951-973.

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Section: Acute Tryptophan Depletionmentioning

confidence: 99%

Monoamine depletion in psychiatric and healthy populations: review

2003

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“…The neuroendocrine response to serotonergic activation has been used as a diagnostic tool to examine the functioning of serotonergic neurons in the brains of patients suffering from mood disorders (Lerer, et al, 1999). The presence of 5-HT 2A receptors in the hypothalamic PVN is supported by autoradiographic (Appel, et al, 1990), in situ hybridization (Gundlah, et al, 1999;Wright, et al, 1995) and immunohistochemical labeling studies (Zhang, et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Sustained treatment with a 5-HT2A receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT2A receptors despite increases in receptor protein levels in rats

Landry

Carrasco

et al. 2008

Neuropharmacology

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SummaryAdaptive changes in serotonin2A (5-HT 2A ) receptor signaling are associated with the clinical response to a number of psychiatric drugs including atypical antipsychotics and selective serotonin reuptake inhibitors. The present study examined possible mechanisms of agonist-induced desensitization of 5-HT 2A receptors in rat hypothalamic paraventricular nucleus (PVN) after 4 and 7 days of treatment with 1 mg/kg (-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The magnitude of 5-HT 2A receptor-mediated oxytocin release decreased 78% after 4 days and 61% after 7 days of DOI treatment. Similarly, the magnitude of ACTH release following 1 mg/kg DOI decreased by 31% after 4 days and 38% after 7 days of DOI treatment. Treatment with DOI for either 4 or 7 days caused a significant decrease (by approximately 50%) in the high affinity 5-HT 2A receptor binding as measured by 125 I-DOI binding compared to saline-treated control rats. In contrast, western blot analysis demonstrated a significant increase in 5-HT 2A receptor protein levels with 4 or 7 days of DOI treatment to 167% and 191% of control levels respectively. Real time quantitative RT-PCR analysis revealed a small but nonsignificant increase in the levels of 5-HT 2A mRNA following treatment with DOI for 4 or 7 days. Taken together, the 5-HT 2A receptor-stimulated hormone responses, agonist binding data and western blot data suggest that although agonist treatment increases the levels of 5-HT 2A receptor protein in the cell membrane, there is a reduction in the population of 5-HT 2A receptors capable of high-affinity binding and mediating a functional response.

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“…Most studies of chronic FX treatment, however, have focused on the neuroendocrine responses to a challenge of the serotonergic system with either 5-hydroxytryptophan (5-HTP), the precursor to 5-HT, or a 5-HT 1A agonist. Compared with controls, an attenuated ACTH and cortisol/corticosterone response to 5-HT 1A activation occurred after chronic FX treatment in humans (18,19) and rats (20 -22). Rats treated with 10 mg/kg FX for 21 d exhibited attenuated ACTH and cortisol responses to a 5-HT 1A agonist (8-OH-DPAT) (21).…”

mentioning

confidence: 99%

“…Rats treated with 10 mg/kg FX for 21 d exhibited attenuated ACTH and cortisol responses to a 5-HT 1A agonist (8-OH-DPAT) (21). The FX-elicited blunting of ACTH and cortisol responses to 5-HT 1A receptor stimulation appears to involve desensitization of postsynaptic 5-HT 1A receptors (19), whereas the antidepressant actions of FX involve desensitization of presynaptic 5-HT 1A autoreceptors (3). Taken together, these studies illustrate that our current knowledge of the effects of FX on the endocrine system without serotoninergic challenge is incomplete.…”

mentioning

confidence: 99%

Chronic Maternal Fluoxetine Infusion in Pregnant Sheep: Effects on the Maternal and Fetal Hypothalamic-Pituitary-Adrenal Axes

Morrison¹,

Riggs

Chien

et al. 2004

Pediatr Res

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Depression during pregnancy is frequently treated with the selective serotonin reuptake inhibitor, fluoxetine (FX). FX increases serotonergic neurotransmission and serotonin plays a role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. We have therefore investigated the effect of chronic administration of FX to the pregnant ewe on the maternal and fetal HPA axes. Nineteen late-gestation sheep were surgically prepared for chronic study of the fetus. FX (n ϭ 7, 98.5 g/kg/d) or sterile water (control, n ϭ 8) was administered to the ewe for 8 d by constant rate i.v. infusion with an initial FX bolus dose of 70 mg. Maternal and fetal plasma ACTH and cortisol concentrations were determined at 0700 h each day. Maternal plasma ACTH concentrations fell on infusion d 2, but no changes were observed in maternal plasma cortisol concentrations. Fetal plasma ACTH concentrations increased on infusion d 7, and fetal plasma cortisol concentrations increased on infusion d 6, 7, and 8 in the FX group. In addition, the regression coefficient for the relationship between fetal ACTH and cortisol levels was significantly greater in the FX group compared with the control group. Thus, maternal FX treatment increased fetal plasma cortisol concentration. These results are of particular interest in the context that exposure of the fetus to excess glucocorticoids at critical windows during development has been shown to increase the risk of poor health outcomes in later life. Clinical depression occurs in 5-15% of pregnant women (1). Treatment of depression during pregnancy is important to fetal outcome by preventing poor maternal self-care and nutrition, disturbed sleep, lack of prenatal care, increased exposure to alcohol and drugs, and a higher risk of suicide by the mother (1). Depression at 28 wk gestation is related to an increase in negative pregnancy outcome, including an increased risk of low-birth-weight newborns, preterm delivery, and small-forgestational-age newborns (2). FX is a SSRI that increases serotonergic neurotransmission and is prescribed clinically for the treatment of depression, obsessive-compulsive disorder, and bulimia (3). It and other SSRIs have become increasingly used for the treatment of depression in pregnancy because of their effectiveness and lower incidence of maternal side effects and wider safety margin compared with tricyclic antidepressants and monoamine oxidase inhibitors (4, 5). However, there have been several reports that use of these drugs during pregnancy can increase the incidence of adverse pregnancy outcomes, including preterm delivery, fetal growth restriction, and poor neonatal adaptation (5-8). There is also evidence for postnatal consequences of prenatal SSRI exposure, including reduced weight gain, slight delays in psychomotor development and motor movement control, and our own findings of reduced facial and heart rate responses to painful stimuli (9 -11). ABSTRACT40

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

Cited by 79 publications

References 61 publications

Monoamine depletion in psychiatric and healthy populations: review

Monoamine depletion in psychiatric and healthy populations: review

Sustained treatment with a 5-HT2A receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT2A receptors despite increases in receptor protein levels in rats

Chronic Maternal Fluoxetine Infusion in Pregnant Sheep: Effects on the Maternal and Fetal Hypothalamic-Pituitary-Adrenal Axes

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