Permanent dopaminergic alterations in the n. accumbens after prenatal stress

doi:10.1016/0091-3057(94)90433-2

Pharmacology Biochemistry and Behavior

Volume 49, Issue 2, October 1994, Pages 353-358

https://doi.org/10.1016/0091-3057(94)90433-2 Get rights and content

Abstract

It has been suggested that stress during the initial stages of human life may serve as a predisposing factor to mental illness. Recently, we reported that in pregnant rats, stress induces an increase of behavioral depression in the female offsprings when adult. This article describes the effect of prenatal stress on central dopaminergic transmission during adulthood. The offspring of stressed mothers showed an increase of behavioral depression in the Porsolt test and a reduction of DOPAC, HVA, and DOPAC/DA index in the n. accumbens. The effect on the right accumbens was more marked than on the left. A great body of information exists to suggest that depression is related to a decrease of dopaminergic neurotransmission, and the present data provide new evidence in support of the hypothesis that maternal stress during gestation increases the risk of depression in the offspring. We are also reporting a hitherto uncommented relationship between behavioral depression in the Porsolt test and the decrease of dopamine transmission in the n. accumbens.

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Elevated rates of dopamine turnover were found in the right prefrontal cortex and reduced dopamine activity in the right nucleus accumbens and left corpus striatum of prenatally stressed animals (Fride and Weinstock, 1988). The offspring of stressed mothers showed an increase of depressive-like behavior in the Porsolt test and a reduction of 3,4-Dihydroxyphenylacetic acid (DOPAC), Homovanillic acid (HVA), and DOPAC/DA index in the n. accumbens, with more pronounced effects in the right accumbens (Alonso et al., 1994). A better and more detailed understanding of the effect of PS on the DAergic system development and function is essential to understand the etiology of psychiatric disorders.
This review focuses on the inter- and transgenerational effects of stress experience prior to and during gestation. We provide an overview of findings from studies in humans as well as in animal models on brain structural and physiological functions and on the development of cognitive and executive functions. We also discuss the concept of stress-induced (re-)programming in more detail by highlighting epigenetic mechanisms and particularly those affecting the development of monoaminergic transmitter systems, which constitute the braińs reward system. As the majority of studies have focused on male individuals we will emphasize sex-specific differences in stress vulnerability and resilience. Finally, we offer some perspectives on the development of protective and therapeutic interventions in cognitive and emotional disturbances resulting from pre-conception and prenatal stress.
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Four observations of the prenatal dataset(striatal Th (Baier et al., 2014), striatal DA (Basta-Kaim et al., 2011), striatal HVA (Ling et al., 2004b), striatal DR2 (Son et al., 2007)) and 6 observations of the postnatal dataset (striatal DR1(Zhang et al., 2013), striatal DR2 (Zhang et al., 2015), DAT in the VTA area (Tien et al., 2013), striatal DOPAC (Ognibene et al., 2008), cortical DA (Matthews et al., 2001) and limbic HVA (Kubesova et al., 2015)) were excluded from the analysis as outliers. The publications included in the analysis were:(Adrover et al., 2007; Alonso et al., 1994; Baharnoori et al., 2013; Baier et al., 2014; Bakos et al., 2004; Basta-Kaim et al., 2011; Berger et al., 2002; Bingham et al., 2013; Bitanihirwe et al., 2010; Brenhouse et al., 2013; Cabib et al., 1993; Cai et al., 2013; Camp et al., 1984; Carboni et al., 2010; Chocyk et al., 2011; Choy et al., 2009; Choy and van den Buuse, 2008; Cory-slechta et al., 2013; Cory-Slechta et al., 2009; Dallé et al., 2016; Delattre et al., 2016; Fan et al., 2011a,b; Gerardin et al., 2005; Gondré-Lewis et al., 2015; Gracia-Rubio et al., 2016; Granholm et al., 2011; Hall et al., 1999; Hensleigh and Pritchard, 2015, 2014; Hermel et al., 2001; Hill et al., 2014; Jahng et al., 2012, 2010; Katunar et al., 2010; Kawakami et al., 2013; Kikusui et al., 2005; Kirsten et al., 2012; Kubesova et al., 2015; Lazzaretti et al., 2015; Lejeune et al., 2013; Li et al., 2014; Ling et al., 2009, 2004a,b; Liu et al., 2016; Lovic et al., 2013; Luchicchi et al., 2016; Madruga et al., 2006; Matthews et al., 2001; Meyer et al., 2008a, 2008b; Novak et al., 2013; Ognibene et al., 2008; Oreland et al., 2011; Ozawa et al., 2006; Pallarés et al., 2013; Panagiotaropoulos et al., 2004; Pang et al., 2015; Papaioannou et al., 2002; Ploj et al., 2003; Rentesi et al., 2013; Reynaert et al., 2016; Reznikov and Nosenko, 1995; Romano-López et al., 2015; Romero et al., 2010, 2007; Rossi-George et al., 2011; Rots et al., 1996; Sasagawa et al., 2017; Silvagni et al., 2008; Silveira et al., 2010; Son et al., 2007; Tien et al., 2013; Vazquez et al., 2007; Vuillermot et al., 2012; Wang et al., 2009; Weston et al., 2014a,b; Winter et al., 2009; Womersley et al., 2011; Zager et al., 2012; Zavitsanou et al., 2013; Zhang et al., 2006, 2015, 2013; Zhu et al., 2011, 2010, 2007; Zuckerman et al., 2003). Substantial heterogeneity was recorded in the prenatal dataset (Q(378) = 954.969, p < 0.001), indicating that our search string identified a diverse range of experiments.
Adverse early life events are a well-established risk factor for the precipitation of behavioral disorders characterized by anomalies in the dopaminergic system, such as schizophrenia and addiction. The correlation between early life conditions and the dopaminergic system has been causally investigated in more than 90 rodent publications. Here, we tested the validity of the hypothesis that early life stress (ELS) alters dopamine signaling by performing an extensive 3-level mixed effect meta-analysis. We included several ELS models and biochemical indicators of the dopaminergic system in a variety of brain areas, for a total of 1009 comparisons. Contrary to our expectations, only a few comparisons displayed a significant effect. Specifically, the striatal area was the most vulnerable, displaying decreased dopamine precursor and increased metabolites after ELS. To make all data openly accessible, we created MaDEapp (https://osf.io/w25m4/), a tool to explore data of the meta-analysis with the intent to guide future (pre)clinical research and allow power calculations. All in all, ELS induces a few yet robust changes on biochemical indicators of the dopaminergic system.
Immature sleep pattern in newborn rats when dams encountered sleep restriction during pregnancy
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In the present study, stress hormones level were not estimated due to practical reasons, but a few reports have indicated adverse effects of increased corticosterone on the hypothalamo-pituitary-adrenal axis activity and gestational stress in the offspring (Takahashi and Kalin, 1991; Weinstock et al., 1992; McCormick et al., 1995; Maccari et al., 1995; Barbazanges et al., 1996). The alteration in development of several neurotransmitters including noradrenaline, dopamine, serotonin and acetylcholine and neuropeptide orexin in the offspring cannot be ruled out (Peters, 1988; Day et al., 1998; Alonso et al., 1994; Yamamoto et al., 2000; Aran et al., 2012). Moreover, prolonged gestation may have a potential role in altering maternal behaviour and foetal changes, as gestation period of the sleep restricted dams was nearly a day longer in comparison to that of the control group rats.
There is a growing realization that proper sleep during pregnancy is essential for the health of the mother and the offspring. However, there are no reports on the effects of maternal sleep restriction on the sleep-wake profiles of newborns. So, this study was conducted to evaluate the effects of sleep restriction during the third term of pregnancy on the sleep-wake profiles of neonates born to them. The female pregnant Wistar rats were sleep restricted for 5 h/day on gestational days 15–20 by gentle handling. Sleep-wake profiles of the pups born to them and to the control rats were recorded on postnatal days 1–21. Pups of sleep restricted dams had higher active sleep (AS) and lower quiet sleep (QS) as well as wakefulness. Higher ratio of AS to QS, longer duration of sleep cycles, lesser bout frequency and reduced EEG delta power were also observed in these pups, all of which indicated brain immaturity. All these signs of delayed maturation, usually found in premature babies, were observed in the pups of sleep restricted mothers, who had longer gestation period. This report not only shows the importance of sleep during pregnancy, but it also suggests that neonatal sleep monitoring can be used as a tool for early assessment of retarded brain development.
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Research on adolescent and adult populations has linked depression to variation in several monoaminergic genes, but genetic association studies on depression in children are limited. Additionally, few studies have investigated whether stressors occurring very early in development moderate the influence of certain genes on depression. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) from monoaminergic genes interacted with measures of early life stress to influence depressive symptoms in children. Participants were members of the Auckland Birthweight Collaborative cohort. Small for gestational age (SGA) and maternal stress during pregnancy were measured at birth and used as indicators of early life stress. At age 11, depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and DNA samples were collected for genotyping. A two-way ANOVA revealed that SGA and a SNP from the dopamine transporter gene DAT1 had an interactive effect on children's depressive symptoms. Specifically, symptoms were greater in children born SGA who are T homozygous for the rs1042098 SNP. These findings suggest that adverse intrauterine environments leading to low birth weight also seem to exacerbate the effects of certain DAT1 variants on depression.
Effect of prenatal stress on memory, nicotine withdrawal and 5HT1A expression in raphe nuclei of adult rats
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The cause of this intensified withdrawal symptom is still unknown. It can be explained by the depletion of dopamine induced by prenatal stress in rats (Alonso et al., 1994), rendering the PS offspring vulnerable to addiction, and helpless against the withdrawal syndrom. Additional non-behavioral observations were reported in this study.
Maternal distress has often been associated with cognitive deficiencies and drug abuse in rats. This study examined these behavioral effects in offspring of mothers stressed during gestation. To this end, pregnant dams were subjected to daily electric foot shocks during the last 10 days of pregnancy. We measured litter parameters and body weights of the descendants after weaning (21 days) and at adulthood (80 days). Afterwards, prenatally stressed and control rats’ performances in the novel object recognition test were compared in order to evaluate their memory while others underwent the Water consumption test to assess the nicotine withdrawal intensity after perinatal manipulations. Meanwhile, another set of rats were sacrificed and 5HT_1A receptors’ mRNA expression was measured in the raphe nuclei by quantitative Real Time PCR. We noticed no significant influence of maternal stress on litter size and body weight right after weaning. However, control rats were heavier than the stressed rats in adulthood. The results also showed a significant decrease in the recognition score in rats stressed in utero compared to the controls. Moreover, a heightened anxiety symptom was observed in the prenatally stressed offspring following nicotine withdrawal. Additionally, the Real Time PCR method revealed that prenatal stress induced a significant decrease in 5HT_1A receptors’ levels in the raphe nuclei. Nicotine had a similar effect on these receptors’ expression in both nicotine-treated control and prenatally stressed groups. Taken together, these findings suggest that the cognitive functions and drug dependence can be triggered by early adverse events in rats.
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for 45 min 3 times on each of these two days at 900, 1200 and 1500 h (Ward and Weisz, 1984). This stress paradigm was chosen because it targets development of key brain structures involved in mediating stress and cognition, including hypothalamic nuclei, hippocampus, striatum and frontal cortex (Weinstock et al., 1998), because of its relatively robust effects, its reported association with changes in mesolimbic dopamine systems (Alonso et al., 1994; Henry et al., 1995; Takahashi et al., 1992) and our prior demonstration of its efficacy in elevating corticosterone in dams (Cory-Slechta et al., 2004). Control or Pb only pregnant females (non-stress groups) were left undisturbed in their home cages.
Both lead (Pb) exposure and prenatal stress (PS) can produce cognitive deficits, and in a prior study we demonstrated enhanced cognitive deficits in repeated learning of female rats exposed to both of these developmental insults (Cory-Slechta et al., 2010). However, PS can also lead to improved cognitive outcomes that are both gender- and context-dependent. Thus, the current study examined whether Pb ± PS likewise produced repeated learning deficits in males, either after maternal or lifetime Pb exposure. Repeated learning was evaluated using a multiple schedule of repeated learning and performance that required learning 3-response sequences in male offspring that had been subjected to either maternal Pb (0 or 150 ppm) or lifetime Pb exposure (0 or 50 ppm) beginning two months prior to dam breeding, to prenatal immobilization restraint stress (gestational days 16–17), or to both Pb and PS. Blood Pb, corticosterone, hippocampal glucocorticoid receptor density and brain monoamines were also measured. In contrast to outcomes in females, sequence-specific enhancements of repeated learning accuracy were produced by PS, particularly when combined with Pb, results that appeared to be more robust in combination with lifetime than maternal Pb exposure. A common behavioral mechanism of these improvements appears to be an increased reinforcement density associated with increased response rates and shorter session times seen with PS ± Pb that could shorten time to reinforcement. Trends toward lower levels of nucleus accumbens dopamine activity seen after both maternal Pb and lifetime Pb combined with PS suggest a possible role for this region/neurotransmitter in enhanced accuracy, whereas PS ± Pb-induced corticosterone changes did not exhibit an obvious systematic relationship to accuracy enhancements. While PS ± Pb-based increases in accuracy appear to be an improved outcome, the benefits of increased response rate are by no means universal, but highly context-dependent and can lead to adverse behavioral effects in other conditions.

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Permanent dopaminergic alterations in the n. accumbens after prenatal stress

Abstract

Physiol. Behav.

Physiol. Behav.

Brain Res.

Brain Res.

Behav. Neural Biol.

Anal. Biochem.

Physiol. Behav.

Life Sci.

Physiol. Behav.

Life Sci.

Neuropsychologia

Pharmacol. Biochem. Behav.

Physiol. Behav.

Brain Res.

J. Chromatogr.

J. Affect. Disord.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Brain Res.

Severe depressive mood changes following slow release intramuscular fluphenazine injection

Br. Med. J.

Behavioral lateralization in rats: Prenatal stress effects on sex differences

Brain Res.

Effect of inescapable shock on subsequent escape performance: Catecholaminergic and cholinergic mediation of response

Psychopharmacology (Berlin)

Is the forced swimming test a suitable model for revealing antidepressant activity?

Psychopharmacology (Berlin)

Precursors and metabolites of 5 hydroxytryptamine and dopamine in the ventricular cerebrospinal fluid of psychiatric patients

Psychol. Med.

Differential catechol-o-methyltransferase activity in unipolar and bipolar affective illness

Arch. Gen. Psychiatry

Pharmacological and biochemical evidence for the dopamine agonistic effect of bromocryptine

Acta Endocrinol. Suppl.

Blood-brain movements of tryptophan and tyrosine in manic-depressve illness and schizophrenia

J. Neural Transm. Suppl.

Ldopa, catecholamines and behavior: A clinical and biochemical study in depressed patients

Biol. Psychiatry

Psychobiological aspects of stress and affective illness