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2.
Front Ecol Evol ; 32016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34055816

RESUMO

A social signal transduction theory of depression has been proposed that states that exposure to social adversity alters the immune response and these changes mediate symptoms of depression such as anhedonia and impairments in social behavior The exposure of maternal rats to the chronic social stress (CSS) of a male intruder depresses maternal care and impairs social behavior in the F1 and F2 offspring of these dams. The objective of the present study was to characterize basal peripheral levels of several immune factors and related hormone levels in the adult F2 offspring of CSS exposed dams and assess whether changes in these factors are associated with previously reported deficits in allogrooming behavior. CSS decreased acid glycoprotein (α1AGP) and intercellular adhesion molecule-1 (ICAM-1) in F2 females, and increased granulocyte macrophage-colony stimulating factor (GM-CSF) in F2 males. There were also sex dependent changes in IL-18, tissue inhibitors of metalloproteinases 1 (TIMP-1), and vascular endothelial growth factor (VEGF). Progesterone was decreased and alpha melanocyte stimulating hormone (α-MSH) was increased in F2 males, and brain-derived neurotrophic factor (BDNF) was decreased in F2 females. Changes in α1AGP, GM-CSF, progesterone, and α-MSH were correlated with decreased allogrooming in the F2 offspring of stressed dams. These results support the hypothesis that transgenerational social stress affects both the immune system and social behavior, and also support previous studies on the adverse effects of early life stress on immune functioning and stress associated immunological disorders, including the increasing prevalence of asthma. The immune system may represent an important transgenerational etiological factor in disorders which involve social and/or early life stress associated changes in social behavior, such as depression, anxiety, and autism, as well as comorbid immune disorders. Future studies involving immune and/or endocrine assessments and manipulations will address specific questions of function and causation, and may identify novel preventative measures and treatments for the growing number of immune mediated disorders.

3.
Behav Pharmacol ; 26(7 Spec No): 642-53, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26061353

RESUMO

Depression and anxiety can be severely detrimental to the health of both the affected woman and her offspring. In a rodent model of postpartum depression and anxiety, chronic social stress exposure during lactation induces deficits in maternal care and increases anxiety. Here, we extend previous findings by expanding the behavioral analyses, assessing lactation, and examining several neural systems within amygdalar and hypothalamic regions involved in the control of the stress response and expression of maternal care that may be mediating the behavioral changes in stressed dams. Compared with control dams, those exposed to chronic social stress beginning on day 2 of lactation show impaired maternal care and lactation and increased maternal anxiety on day 9 of lactation. Saccharin-based anhedonia and maternal aggression were increased and lactation was also impaired on day 16 of lactation. These behavioral changes were correlated with a decrease in oxytocin mRNA expression in the medial amygdala, and increases in the expressions of corticotrophin-releasing hormone mRNA in the central nucleus of the amygdala, glucocorticoid receptor mRNA in the paraventricular nucleus, and orexin 2 receptor mRNA in the supraoptic nucleus of stressed compared with control dams. The increase in glucocorticoid receptor mRNA in the paraventricular nucleus was negatively correlated with methylation of a CpG site in the promoter region. In conclusion, the data support the hypothesis that social stress during lactation can have profound effects on maternal care, lactation, and anxiety, and that these behavioral effects are mediated by central changes in stress and maternally relevant neuropeptide systems.


Assuntos
Encéfalo/metabolismo , Comportamento Materno/fisiologia , Comportamento Materno/psicologia , Comportamento Social , Estresse Psicológico/fisiopatologia , Agressão/fisiologia , Agressão/psicologia , Anedonia/fisiologia , Animais , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/psicologia , Doença Crônica , Depressão Pós-Parto/fisiopatologia , Depressão Pós-Parto/psicologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Lactação/fisiologia , Lactação/psicologia , Receptores de Orexina/metabolismo , Ocitocina/metabolismo , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Sacarina , Percepção Gustatória/fisiologia
4.
Horm Behav ; 65(4): 386-93, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24657520

RESUMO

Social stressors such as depressed maternal care and family conflict are robust challenges which can have long-term physiological and behavioral effects on offspring and future generations. The current study investigates the transgenerational effects of an ethologically relevant chronic social stress on the behavior and endocrinology of juvenile and adult rats. Exposure to chronic social stress during lactation impairs maternal care in F0 lactating dams and the maternal care of the F1 offspring of those stressed F0 dams. The overall hypothesis was that the male and female F2 offspring of stressed F1 dams would display decreased social behavior as both juveniles and adults and that these behavioral effects would be accompanied by changes in plasma corticosterone, prolactin, and oxytocin. Both the female and male F2 offspring of dams exposed to chronic social stress displayed decreased social behavior as juveniles and adults, and these behavioral effects were accompanied by decreases in basal concentrations of corticosterone in both sexes, as well as elevated juvenile oxytocin and decreased adult prolactin in the female offspring. The data support the conclusion that social stress has transgenerational effects on the social behavior of the female and male offspring which are mediated by changes in the hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis. Social stress models are valuable resources in the study of the transgenerational effects of stress on the behavioral endocrinology of disorders such as depression, anxiety, autism, and other disorders involving disrupted social behavior.


Assuntos
Comportamento Animal/fisiologia , Corticosterona/sangue , Ocitocina/sangue , Prolactina/sangue , Comportamento Social , Estresse Psicológico/fisiopatologia , Fatores Etários , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/sangue
5.
Behav Pharmacol ; 25(2): 173-81, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24561499

RESUMO

Prescription opiate use by adolescent girls has increased significantly in the past decade. Preclinical studies using rats report alterations in morphine sensitivity in the adult offspring of adolescent morphine-exposed females (MOR-F1) when compared with the offspring of adolescent saline-exposed females (SAL-F1). To begin to elucidate the development of these next generation modifications, the present study examined the effects of acute morphine administration on sedation and corticosterone secretion in prepubescent SAL-F1 and MOR-F1 male and female rats. In addition, alterations in proopiomelanocortin (POMC) gene expression in the arcuate nucleus, as well as in tyrosine hydroxylase (TH) and µ-opioid receptor (OPRM1) gene expressions in the ventral tegmental area, were analyzed using quantitative PCR, to determine whether differential regulation of these genes was correlated with the observed behavioral and/or endocrine effects. Increased morphine-induced sedation, coupled with an attenuation of morphine-induced corticosterone secretion, was observed in MOR-F1 males. Significant alterations in both POMC and OPRM1 gene expressions were also observed in MOR-F1 males, with no change in TH mRNA expression. Overall, these data suggest that the transgenerational effects of adolescent morphine exposure can be discerned before pubertal development and are more pronounced in males, and suggest dysregulation of the hypothalamic-pituitary-adrenal axis in the offspring of adolescent morphine-exposed females.


Assuntos
Exposição Materna , Morfina/farmacologia , Entorpecentes/farmacologia , Maturidade Sexual/efeitos dos fármacos , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/crescimento & desenvolvimento , Núcleo Arqueado do Hipotálamo/fisiologia , Corticosterona/sangue , Corticosterona/metabolismo , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Pró-Opiomelanocortina/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/metabolismo , Caracteres Sexuais , Maturidade Sexual/fisiologia , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/crescimento & desenvolvimento , Área Tegmentar Ventral/fisiologia
6.
Horm Behav ; 64(4): 634-41, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24005186

RESUMO

Exposure to early life stress is a predictor of mental health disorders, and two common forms of early life stress are social conflict and impaired maternal care, which are predominant features of postpartum mood disorders. Exposure of lactating female rats to a novel male intruder involves robust social conflict and induces deficits in maternal care towards the F1 offspring. This exposure is an early life social stressor for female F1 pups that induces inefficient lactation associated with central changes in oxytocin (OXT), prolactin (PRL), and arginine vasopressin (AVP) gene expression in adult F1 females. The mothers of the rats in the current study were either allowed to raise their pups without exposure to a social stressor (control), or presented with a novel male intruder for 1h each day on lactation days 2-16 (chronic social stress). The effects of this early life chronic social stress (CSS) exposure on subsequent peripheral endocrinology, maternal behavior, and physiology were assessed. Exposure of female pups to early life CSS resulted in persistent alterations in maternal endocrinology at the end of lactation (attenuated prolactin and elevated corticosterone), depressed maternal care and aggression, increased restlessness and anxiety-related behavior, impaired lactation, and decreased saccharin preference. The endocrine and behavioral data indicate that early life CSS has long-term effects which are similar to changes seen in clinical populations of depressed mothers and provide support for the use of the chronic social stress paradigm as an ethologically relevant rodent model for maternal disorders such as postpartum depression and anxiety.


Assuntos
Hormônios/sangue , Lactação/fisiologia , Comportamento Materno , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico , Agressão/fisiologia , Animais , Animais Recém-Nascidos , Corticosterona/sangue , Feminino , Masculino , Comportamento Materno/fisiologia , Comportamento Materno/psicologia , Ocitocina/sangue , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/psicologia , Prolactina/sangue , Ratos , Comportamento Social , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia
7.
J Vis Exp ; (76): e50324, 2013 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-23792810

RESUMO

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.


Assuntos
Depressão Pós-Parto , Modelos Animais de Doenças , Estresse Psicológico , Animais , Comportamento Animal , Doença Crônica , Feminino , Lactação , Masculino , Ratos , Ratos Sprague-Dawley
8.
Psychopharmacology (Berl) ; 227(2): 263-72, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23314440

RESUMO

RATIONALE: The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring. OBJECTIVES: In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure. METHODS: We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generations) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine. RESULTS: Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion and upregulated kappa opioid receptor and dopamine D2 receptor (D2R) gene expression within the nucleus accumbens. CONCLUSIONS: These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.


Assuntos
Analgésicos Opioides/farmacologia , Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Receptores de Dopamina D2/metabolismo , Fatores Etários , Analgésicos Opioides/administração & dosagem , Animais , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/farmacologia , Epigênese Genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Morfina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Quimpirol/administração & dosagem , Quimpirol/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D2/genética
9.
Behav Brain Res ; 223(2): 322-8, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21571006

RESUMO

Prior studies have supported a role for mesolimbic dopaminergic mechanisms in the regulation of maternal behavior. Accordingly, the ventral tegmental area (VTA) and its dopaminergic projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in both the onset and maintenance of normal maternal behavior. To date, studies of direct manipulation of VTA neurochemistry at the onset of maternal behavior have been limited. The current study was undertaken to directly test the hypothesis that enhancement of dopaminergic transmission in the mesolimbic dopamine system can stimulate maternal activity using a pup-induced virgin model. Nulliparous female rats were stereotaxically infused with pertussis toxin (PTX 0, 0.1, or 0.3 µg/hemisphere) into the VTA to chronically stimulate the activity of dopaminergic projection neurons. After 3 days of recovery, maternal responding to donor pups was tested daily, and latency (in days) to full maternal behavior was recorded. Intra-VTA PTX treatment produced a robust dose-dependent decrease in maternal behavior latency, and a long-lasting increase in locomotor activity. These effects were associated with significantly decreased dopamine D1 receptor mRNA expression in the NAc. No effects of PTX treatment on mesolimbic dopamine utilization or mPFC receptor expression were observed. The findings indicate that chronic neural activation in the VTA accelerates the onset of maternal behavior in virgin female rats via modification of the NAc dopamine D1 receptor.


Assuntos
Comportamento Materno/efeitos dos fármacos , Toxina Pertussis/farmacologia , Área Tegmentar Ventral/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Química Encefálica/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Dopamina/metabolismo , Feminino , Microinjeções , Atividade Motora/efeitos dos fármacos , Toxina Pertussis/administração & dosagem , Prosencéfalo/metabolismo , Prosencéfalo/fisiologia , RNA/biossíntese , RNA/genética , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/biossíntese , Receptores de Dopamina D1/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Técnicas Estereotáxicas
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