Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring

Huether, Gerald; Thömke, Frank; Adler, Lothar

doi:10.1016/0165-3806(92)90059-6

Cited by 41 publications

(18 citation statements)

References 36 publications

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“…During development, serotonin receptors may be more susceptible to down-regulation than in the adult. In rats, increased serotonin concentrations during pregnancy induced through a tryptophan-enriched diet or through 5-methoxytryptophan treatment delays serotonin axon outgrowth and/or decreases collateral sprouting, synapse formation, and induces receptor downregulation (49,50). Pharmacodynamic modelling was performed to determine whether there was a relationship between maternal or fetal FX concentrations and ACTH or cortisol concentrations but no correlations were found (data not shown).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…169 Several drug treatment studies have shown this negative feedback of 5-HT on development of 5-HTergic neurons. [170][171][172][173][174][175][176][177][178][179][180] Alterations in 5-HTT function 181 and hypothalamic 5-HT levels 182 may be in part responsible for altered HPA axis activity in adult PS offspring. 183 PS may lead to an altered set-point of the HPA axis and 5-HT system, increasing susceptibility to later (depressive) disorders.…”

Section: Stressmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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“…5HT, NE, and DA) systems (2,3), such as cell migration, axonal outgrowth, and synaptogenesis, coordinating mediators of intercellular communication (4,5), and modulation of respiratory rhythm (6) in the developing fetus, (7)(8)(9)(10). The trophic action of GABA, mediated by GABAa receptors, on developing neurons (see Ref.…”

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confidence: 99%

Prolonged Prenatal Psychotropic Medication Exposure Alters Neonatal Acute Pain Response

et al. 2002

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Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are frequently used to treat maternal depression during pregnancy, however the effect of increased serotonin (5HT) and ␥-amino-butyric acid (GABA) agonists in the fetal human brain remains unknown. 5HT and GABA are active during fetal neurologic growth and play early roles in pain modulation, therefore, if prolonged prenatal exposure alters neurodevelopment this may become evident in altered neonatal pain responses. To examine biologic and behavioral effects of prenatal exposure, neonatal responses to acute pain (phenylketonuria heel lance) in infants with prolonged prenatal exposure were examined. Facial action (Neonatal Facial Coding System) and cardiac autonomic reactivity derived from the relationship between respiratory activity and short term variations of heart rate (HRV) were compared between 22 infants with SSRI exposure (SE) [fluoxetine (n ϭ 7), paroxetine (n ϭ 11), sertraline (n ϭ 4)]; 16 infants exposed to SSRIs and clonazepam (SEϩ) [paroxetine (n ϭ 14), fluoxetine (n ϭ 2)]; and 23 nonexposed infants during baseline, lance, and recovery periods of a heel lance. Length of maternal SSRI use did not vary significantly between exposure groups-[mean (range)] SE:SEϩ 183 (31-281):141 (54 -282) d (p Ͼ 0.05). Infants exposed to SE and SEϩ displayed significantly less facial activity to heel lance than control infants. Mean HR increased with lance, but was significantly lower in SE infants during recovery. Using measures of HRV and the transfer relationship between heart rate and respiration, SSRI infants had a greater return of parasympathetic cardiac modulation in the recovery period, whereas a sustained sympathetic response continued in the control group. Prolonged prenatal SSRI exposure appears to be associated with reduced behavioral pain responses and increased parasympathetic cardiac modulation in recovery following an acute neonatal noxious event. Possible 5HT-mediated pain inhibition, pharmacologic factors and the developmental course remain to be studied. (Pediatr Res 51: 443-453, 2002) Abbreviations 5HT, 5 hydroxytryptamine (serotonin) BZ, benzodiazepine C, control (nonexposed) infants DA, dopamine GABA, ␥-amino-butyric acid HFP, high-frequency power HRV, heart rate variability LFP, low-frequency power NE, norepinephrine NFCS, Neonatal Facial Coding System NICU, neonatal intensive care unit PKU, phenylketonuria RP, respiratory power RSA, respiratory sinus arrhythmia SE, SSRI-exposed infants SE؉, SSRI-and BZ-exposed infants SSRI, selective serotonin reuptake inhibitors Maternal anxiety and depression are frequently treated during pregnancy with psychotropic medications such as SSRIs and BZs (1). Given that all psychotropic medications diffuse easily across the placenta, clinicians caring for women with psychiatric illness during their pregnancies are faced with the difficult task of making recommendations regarding psychotropic medication use with unknown effects on the growing fetus. To date, none of these medications have been appr...

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Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring

Cited by 41 publications

References 36 publications

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

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

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Prolonged Prenatal Psychotropic Medication Exposure Alters Neonatal Acute Pain Response

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