44 research outputs found

    Dopaminergic modulation of affective and social deficits induced by prenatal glucocorticoid exposure

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    Prenatal stress or exposure to elevated levels of glucocorticoids (GCs) can impair specific neurobehavioral circuits leading to alterations in emotional processes later in life. In turn, emotional deficits may interfere with the quality and degree of social interaction. Here, by using a comprehensive behavioral approach in combination with the measurement of ultrasonic vocalizations, we show that in utero GC (iuGC)-exposed animals present increased immobility in the forced swimming test, pronounced anhedonic behavior (both anticipatory and consummatory), and an impairment in social interaction at different life stages. Importantly, we also found that social behavioral expression is highly dependent on the affective status of the partner. A profound reduction in mesolimbic dopaminergic transmission was found in iuGC animals, suggesting a key role for dopamine (DA) in the etiology of the observed behavioral deficits. Confirming this idea, we present evidence that a simple pharmacological approach—acute L-3,4-dihydroxyphenylacetic acid (L-DOPA) oral administration, is able to normalize DA levels in iuGC animals, with a concomitant amelioration of several dimensions of the emotional and social behaviors. Interestingly, L-DOPA effects in control individuals were not so straightforward; suggesting that both hypo- and hyperdopaminergia are detrimental in the context of such complex behaviors.This work was supported by a grant of Institute for the Study of Affective Neuroscience (ISAN) and Janssen Neurosciences Prize. SB and AJR have Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/89936/2012; SFRH/BPD/33611/2009)

    Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

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    Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity

    Behav. Brain Res.

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    The reliability of behavioural data constitutes a major concern in the neuroscience field. Indeed, discrepancies in the behavioural patterns of mice or rats in the same anxiety tests performed in different laboratories have been reported recently. The question raised by such data addressed, in particular, the selection and breeding of two lines of rats on the basis of their high (HAB) and low (LAB) anxiety-related behaviour in the elevated plus-maze test at the Max Planck Institute of Psychiatry in Munich (Germany). As the majority of the behavioural data in these animals has been derived from research carried out in this institute, the aims of the present study were: (1) to test the reliability of the differences in anxiety-related behaviour of these rats in two other laboratories (Villeneuve d''Ascq, France and Innsbruck, Austria); and (2) to determine how the different behavioural traits were associated in both HAB and LAB rats by a principal component analysis. Results were in agreement with the studies performed in Munich, as the divergence in anxiety-related behaviour of the two lines was highly consistent in all tests performed in Villeneuve d''Ascq and Innsbruck. Moreover, the most important parameters to discriminate the two lines were similar to those found in a previous study. Finally, the principal component analysis again confirmed that the selection of HAB and LAB rats is based on anxiety-related behaviour rather than locomotor activity. (C) 2002 Elsevier Science B.V. All rights reserv

    Reliability of high and low anxiety-related behaviour: influence of laboratory environment and multifactorial analysis

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    The reliability of behavioural data constitutes a major concern in the neuroscience field. Indeed, discrepancies in the behavioural patterns of mice or rats in the same anxiety tests performed in different laboratories have been reported recently. The question raised by such data addressed, in particular, the selection and breeding of two lines of rats on the basis of their high (HAB) and low (LAB) anxiety-related behaviour in the elevated plus-maze test at the Max Planck Institute of Psychiatry in Munich (Germany). As the majority of the behavioural data in these animals has been derived from research carried out in this institute, the aims of the present study were: (1) to test the reliability of the differences in anxiety-related behaviour of these rats in two other laboratories (Villeneuve d''Ascq, France and Innsbruck, Austria); and (2) to determine how the different behavioural traits were associated in both HAB and LAB rats by a principal component analysis. Results were in agreement with the studies performed in Munich, as the divergence in anxiety-related behaviour of the two lines was highly consistent in all tests performed in Villeneuve d''Ascq and Innsbruck. Moreover, the most important parameters to discriminate the two lines were similar to those found in a previous study. Finally, the principal component analysis again confirmed that the selection of HAB and LAB rats is based on anxiety-related behaviour rather than locomotor activity. (C) 2002 Elsevier Science B.V. All rights reserv

    Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats.

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    Prenatal stress in the rat induces enhanced reactivity of the hypothalamus-pituitary-adrenal (HPA) axis, disturbances in a variety of circadian rhythms and increased anxiety-like behaviour. Such abnormalities parallel those found in human depressed patients. Prenatally stressed (PS) rats could represent, therefore, an interesting animal model for the evaluation of the efficacy of pharmacotherapeutic intervention in psychiatric disorders that has often been addressed using control animals. In the present study, PS and non-stressed rats were chronically treated with the tricyclic antidepressant imipramine (10 mg/kg i.p. for 21 days) and assessed in the forced swim test. Glucocorticoid receptor binding sites in the hippocampus were measured and 5-HT(1A) receptor mRNA levels in the frontal cortex were also assessed. PS rats were characterised by increased immobility in the forced swim test, reduced hippocampal corticosteroid receptor binding and increased levels of cortical 5-HT(1A) mRNA. All these parameters were significantly reversed by chronic imipramine treatment. Conversely, no significant effects were observed for non-stressed rats. All these effects are consistent with the expected pharmacotherapy of depression-like abnormalities in PS rats. These results further indicate that PS rats are a relevant animal model of depression
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