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learned helplessness

Masaaki Iwata, Hisahito Ishida, Koichi Kaneko, Yukihiko Shirayama
An accumulating body of evidence has demonstrated that inflammation is associated with the pathology of depression. We recently found that psychological stress induces inflammation in the hippocampus of the rat brain through the inflammasome, a component of the innate immune system. Microglia, the resident macrophages in the brain, play a central role in the innate immune system and express inflammasomes; thus, we hypothesized that hippocampal microglia would be key mediators in the development of depression via stress-induced inflammation...
October 18, 2016: Pharmacology, Biochemistry, and Behavior
Agnieszka Mika, Heidi E Day, Alexander Martinez, Nicole L Rumian, Benjamin N Greenwood, Maciej Chichlowski, Brian M Berg, Monika Fleshner
Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health- promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviors such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioral and biological responses to stress later in life...
October 20, 2016: European Journal of Neuroscience
Steven F Grieco, Dmitry Velmeshev, Marco Magistri, Hagit Eldar-Finkelman, Mohammad A Faghihi, Richard S Jope, Eleonore Beurel
OBJECTIVES: We examined mechanisms that contribute to the rapid antidepressant effect of ketamine in mice that is dependent on glycogen synthase kinase-3 (GSK3) inhibition. METHODS: We measured serotonergic (5HT)-2C-receptor (5HTR2C) cluster microRNA (miRNA) levels in mouse hippocampus after administering an antidepressant dose of ketamine (10 mg/kg) in wild-type and GSK3 knockin mice, after GSK3 inhibition with L803-mts, and in learned helpless mice. RESULTS: Ketamine up-regulated cluster miRNAs 448-3p, 764-5p, 1264-3p, 1298-5p and 1912-3p (2- to 11-fold)...
October 10, 2016: World Journal of Biological Psychiatry
Gayaprasad Upadhyay, Sarvesh Khoshla, Ramoji Kosuru, Sanjay Singh
OBJECTIVE: The current study was designed to explore anxiolytic, antidepressant, and antistress actions of Cinnamomum tamala (CT) leaves (aqueous extract) in rats. MATERIALS AND METHODS: Behavioral procedures of anxiety, depression, and stress were assessed in rats. CT (100, 200, and 400 mg/kg) was given once a daily for 7 days via oral route and the efficacy was matched by those elicited by lorazepam (1 mg/kg, p.o.), imipramine (10 mg/kg, p.o.), and Withania somnifera (100 mg/kg, p...
September 2016: Indian Journal of Pharmacology
Ebru Salcioglu, Sevim Urhan, Tugba Pirinccioglu, Sule Aydin
Objective: Embracing the conceptual framework of contemporary learning theory, this study tested the hypothesis that anticipatory fear due to a sense of ongoing threat to safety and sense of helplessness in life would be the strongest determinants of PTSD and depression in domestic violence survivors. Method: Participants were 220 domestic violence survivors recruited consecutively from 12 shelters for women in Turkey (response rate 70%). They were assessed with the Semi-Structured Interview for Survivors of Domestic Violence, Traumatic Stress Symptom Checklist, Depression Rating Scale, and Fear and Sense of Control Scale...
October 6, 2016: Psychological Trauma: Theory, Research, Practice and Policy
Xin Yin, Nuri Guven, Nikolas Dietis
Depression is one of the leading causes of disability and a significant health-concern worldwide. Much of our current understanding on the pathogenesis of depression and the pharmacology of antidepressant drugs is based on pre-clinical models. Three of the most popular stress-based rodent models are the forced swimming test, the chronic mild stress paradigm and the learned helplessness model. Despite their recognizable advantages and limitations, they are associated with an immense variability due to the high number of design parameters that define them...
September 20, 2016: Brain Research
É Cappe, N Poirier, É Boujut, N Nader-Grosbois, C Dionne, A Boulard
INTRODUCTION: Autism and related disorders are grouped into the category of « Autism Spectrum Disorder » (ASD) in the DSM-5. This appellation reflects the idea of a dimensional representation of autism that combines symptoms and characteristics that vary in severity and intensity. Despite common characteristics, there are varying degrees in intensity and in the onset of symptoms, ranging from a disability that can be very heavy with a total lack of communication and major disorders associated with the existence of a relative autonomy associated, sometimes, with extraordinary intellectual abilities...
September 9, 2016: L'Encéphale
Jeffery N Talbot, Laura M Geffert, Jessica E Jorvig, Ruben I Goldstein, Cienna L Nielsen, Nicholas E Wolters, Mary Ellen Amos, Caitlin A Munro, Elizabeth Dallman, Maddalena Mereu, Gianluigi Tanda, Jonathan L Katz, Martín Indarte, Jeffry D Madura, Hailey Choi, Rehana K Leak, Christopher K Surratt
Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests)...
August 26, 2016: Pharmacology, Biochemistry, and Behavior
Dongmei Li, Ji Zheng, Mingyang Wang, Lu Feng, Zhili Ren, Yanyong Liu, Nan Yang, Pingping Zuo
Low response rate was witnessed with the present monoaminergic based antidepressants, urging a need for new therapeutic target identification. Accumulated evidences strongly suggest that mitochondrial deficit is implicated in major depression and 18kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function. However the changes of TSPO and TSPO mediated mitophagy pathway in the depressive brain is unclear. In present study, a well validated animal model of depression, learned helplessness (LH), was employed to investigate the relevant changes...
November 30, 2016: Psychiatry Research
Steven F Grieco, Yuyan Cheng, Hagit Eldar-Finkelman, Richard S Jope, Eléonore Beurel
An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness...
January 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Lei An, Ji-Chu Yang, Hang Yin, Rui Xue, Qiong Wang, Yu Chen Sun, You-Zhi Zhang, Ming Yang
Yacon (Smallanthus sonchifolius), a traditional food in the Andean diet, is attracting global attention for its medicinal properties, which are mainly because of its high content of non-digestible oligosaccharides. The purpose of this study is to evaluate the antidepressant-like effects of inulin-type oligosaccharides extracted from yacon (YOs) in behavioral models of depression. Behavioral despair models in mice including the tail suspension test (TST) and the forced swimming test (FST) were used to determine the effects of acute YOs administration...
August 19, 2016: Phytotherapy Research: PTR
Joanes Grandjean, Damiano Azzinnari, Aline Seuwen, Hannes Sigrist, Erich Seifritz, Christopher R Pryce, Markus Rudin
Human depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward...
August 9, 2016: NeuroImage
P Campus, M Maiolati, C Orsini, S Cabib
Genetic and stress-related factors interact to foster mental disorders, possibly through dysfunctional learning. In a previous study we reported that a temporary experience of reduced food availability increases forced swim (FS)-induced helplessness tested 14days after a first experience in mice of the standard inbred C57BL/6(B6) strain but reduces it in mice of the genetically unrelated DBA/2J (D2) strain. Because persistence of FS-induced helplessness influences adaptive coping with stress challenge and involve learning processes the present study tested whether the behavioral effects of restricted feeding involved altered consolidation of FS-related learning...
December 15, 2016: Behavioural Brain Research
Katrine Svenningsen, Morten T Venø, Kim Henningsen, Anne S Mallien, Line Jensen, Trine Christensen, Jørgen Kjems, Barbara Vollmayr, Ove Wiborg
Depression is a highly heterogeneous disorder presumably caused by a combination of several factors ultimately causing the pathological condition. The genetic liability model of depression is likely to be of polygenic heterogeneity. miRNAs can regulate multiple genes simultaneously and therefore are candidates that align with this model. The habenula has been linked to depression in both clinical and animal studies, shifting interest towards this region as a neural substrate in depression. The goal of the present study was to search for alterations in miRNA expression levels in the medial and lateral habenula of rats exposed to the learned helplessness (LH) rat model of depression...
2016: PloS One
Ying Yang, Zhi-Hao Wang, Sen Jin, Di Gao, Nan Liu, Shan-Ping Chen, Sinan Zhang, Qing Liu, Enjie Liu, Xin Wang, Xiao Liang, Pengfei Wei, Xiaoguang Li, Yin Li, Chenyu Yue, Hong-Lian Li, Ya-Li Wang, Qun Wang, Dan Ke, Qingguo Xie, Fuqiang Xu, Liping Wang, Jian-Zhi Wang
Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection...
2016: Nature Communications
Julia Rummel, Mareike Voget, Ravit Hadar, Samuel Ewing, Reinhard Sohr, Julia Klein, Alexander Sartorius, Andreas Heinz, Aleksander A Mathé, Barbara Vollmayr, Christine Winter
Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy-refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease...
October 2016: Journal of Psychiatric Research
Steven F Maier, Martin E P Seligman
Learned helplessness, the failure to escape shock induced by uncontrollable aversive events, was discovered half a century ago. Seligman and Maier (1967) theorized that animals learned that outcomes were independent of their responses-that nothing they did mattered-and that this learning undermined trying to escape. The mechanism of learned helplessness is now very well-charted biologically, and the original theory got it backward. Passivity in response to shock is not learned. It is the default, unlearned response to prolonged aversive events and it is mediated by the serotonergic activity of the dorsal raphe nucleus, which in turn inhibits escape...
July 2016: Psychological Review
Joseph Bernstein
No abstract text is available yet for this article.
September 2016: Clinical Orthopaedics and related Research
N E Ordyan, S G Pivina, V V Rakitskaya, V K Akulova
The hypothalamic-pituitary-adrenal (HPA) axis activity changes were examined in the adult, prenatally stressed male rats in the experimental depression model--the paradigm of "learned helplessness". It was shown that in males descending from intact mothers a depressive-like state was accompanied by an increase in HPA activity. The expression of corticotrophin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) increases, coupled with a rise in plasma levels of ACTH and corticosterone as well as in adrenal weight...
January 2016: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
Qiong-Yin Fan, Rui Xue, Ying Li, Ting-Ting Zhang, Xin-Hua He, Shi-Yong Fan, Yun-Feng Li, Bo-Hua Zhong, You-Zhi Zhang, Jin Li
AIMS: The present study was conducted to evaluate the antidepressant-like effects of ZBH2012001, a novel potential serotonin and norepinephrine reuptake inhibitor (SNRI). METHODS: Competitive binding assays, calcium flow, and cAMP detection methods were used to determine the affinity of ZBH2012001 for serotonin transporters (SERTs) and norepinephrine transporters (NETs), as well as its selectivity over dopamine transporters (DATs) and 16 other G-protein-coupled receptors (GPCRs) or iron channels...
August 2016: CNS Neuroscience & Therapeutics
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