Depressive behavior and activation of the orexin/hypocretin system.

Arendt, David H.; Ronan, Patrick J.; Oliver, Kevin D; Callahan, Leah; Summers, Tangi R.; Summers, Cliff H.

doi:10.1037/a0031442

Cited by 72 publications

(51 citation statements)

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“…The intensity gradient for anxious behavior was modifiable by a variety of neuromodulatory systems, which include CRF, NPS, NE, as well as Orx and 5-HT, known to modify anxious behavior and synergistically interact within the appropriate circuits (Arendt et al, 2014; Arendt et al, 2013; Cannella et al, 2013; Jungling et al, 2008; Li et al, 2015; Orsini and Maren, 2012; Smith et al, 2014). The results of experiments utilizing the SAM apparatus suggest that in addition to Pavlovian fear conditioning and decision-making (Smith et al, 2014), this model is an effective way to examine the escalation of anxious behavior as environmentally and socially relevant contextual events amplify the intensity of emotional response along a gradient of anxiety (Figure 1C).…”

Section: Discussionmentioning

confidence: 99%

“…The intra-amygdalar fear/anxiety circuitry includes a glutamatergic pyramidal circuit (lateral = LA, basolateral = BLA) modified by GABAergic modulation and output (BLA, intercalated, CeA), both additionally modified by CRF, orexin (Orx), NPS, norepinephrine (NE), and serotonin (5-HT). There is strong evidence for modification of anxious behavior, and synergistic cross-talk among transmitter and neuromodulatory elements in this circuit (Arendt et al, 2014; Arendt et al, 2013; Cannella et al, 2013; Jungling et al, 2008; Li et al, 2015; Orsini and Maren, 2012; Smith et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Intensity of anxiety is modified via complex integrative stress circuitries

Smith

Prince

Achua

et al. 2016

Psychoneuroendocrinology

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Summary Escalation of anxious behavior while environmentally and socially relevant contextual events amplify the intensity of emotional response produces a testable gradient of anxiety shaped by integrative circuitries. Apprehension of the Stress-Alternatives Model apparatus (SAM) oval open field (OF) is measured by the active latency to escape, and is delayed by unfamiliarity with the passageway. Familiar OF escape is the least anxious behavior along the continuum, which can be reduced by anxiolytics such as icv neuropeptide S (NPS). Social aggression increases anxiousness in the SAM, reducing the number of mice willing to escape by 50%. The apprehension accompanying escape during social aggression is diminished by anxiolytics, such as exercise and corticotropin releasing-factor receptor 1 (CRF1) antagonism, but exacerbated by anxiogenic treatment, like antagonism of α2-adrenoreceptors. What is more, the anxiolytic CRF1 and anxiogenic α2-adrenoreceptor antagonists also modify behavioral phenotypes, with CRF1 antagonism allowing escape by previously submissive animals, and α2-adrenoreceptor antagonism hindering escape in mice that previously engaged in it. Gene expression of NPS and brain-derived neurotrophic factor (BDNF) in the central amygdala (CeA), as well as corticosterone secretion, increased concomitantly with the escalating anxious content of the mouse-specific anxiety continuum. The general trend of CeA NPS and BDNF expression suggested that NPS production was promoted by increasing anxiousness, and that BDNF synthesis was associated with learning about ever-more anxious conditions. The intensity gradient for anxious behavior resulting from varying contextual conditions may yield an improved conceptualization of the complexity of mechanisms producing the natural continuum of human anxious conditions, and potential therapies that arise therefrom.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intensity of anxiety is modified via complex integrative stress circuitries

Smith

Prince

Achua

et al. 2016

Psychoneuroendocrinology

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“…OXergic cells project to many brain regions that are involved in regulating mood and anxiety (Peyron et al, 1998), and where the expression of OX1R has been confirmed in nocturnal laboratory rats (Trivedi et al, 1998, Lu et al, 2000, Hervieu et al, 2001, Sunter et al, 2001). The involvement of the OXA-OX1R pathway in these sites has been assessed in various animal models of depression (Feng et al, 2007, Feng et al, 2008, Nocjar et al, 2012, Arendt et al, 2013). For example, in a social defeat model, reduced OXA levels were found in VTA and mPFC in defeated animals compared to undefeated controls (Nocjar et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Attenuated orexinergic signaling underlies depression-like responses induced by daytime light deficiency

Deats¹,

Adidharma²,

Lonstein³

et al. 2014

Neuroscience

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Light has profound effects on mood, as exemplified by seasonal affective disorder (SAD) and the beneficial effects of bright light therapy. However, the underlying neural pathways through which light regulates mood are not well understood. Our previous work has developed the diurnal grass rat, Arvicanthis niloticus, as an animal model of SAD (Leach et al., 2013a, Leach et al., 2013b). By utilizing a 12:12hr Dim Light:Dark (DLD) paradigm that simulates the lower light intensity of winter, we showed that the animals housed in DLD exhibited increased depression-like behaviors in the forced swim test (FST) and sweet solution preference (SSP) compared to animals housed in bright light during the day (BLD). The objective of the present study was to test the hypothesis that light affects mood by acting on the brain orexinergic system in the diurnal grass rat model of SAD. First, orexinA immunoreactivity (OXA-ir) was examined in DLD and BLD grass rats. The results revealed a reduction in the number of OXA-ir neurons in the hypothalamus and attenuated OXA-ir fiber density in the dorsal raphe nucleus of animals in the DLD compared to those in the BLD group. Then, the animals in BLD were treated systemically with SB-334867, a selective orexin 1 receptor (OX1R) antagonist, which led to a depressive phenotype characterized by increased immobility in the FST and a decrease in SSP compared to vehicle-treated controls. The results suggest that attenuated orexinergic signaling is associated with increased depression-like behaviors in grass rats, and support the hypothesis that the orexinergic system mediates the effects of light on mood.

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“…A Leu72Met polymorphism in the ghrelin gene coding region associates with depression (Nakashima et al, 2008), and elevated ghrelin levels have been found in patients with treatment-resistant depression (Ishitobi et al, 2012), suggesting that ghrelin may be a useful indicator of treatment efficacy. In addition, the orexin system, including the expression of orexin and its receptors (Ox1R and Ox2R) has been implicated in the expression of both maternal care (D'Anna and Gammie, 2006) and depressive behavior and pathophysiology (Arendt et al, 2013; Nollet and Leman, 2013). The clinical and rodent studies indicate that ghrelin and orexin may mediate the depressed maternal care in dams exposed to ECSS.…”

Section: Introductionmentioning

confidence: 99%

Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care

et al. 2015

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Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS )based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring.

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Depressive behavior and activation of the orexin/hypocretin system.

Cited by 72 publications

References 50 publications

Intensity of anxiety is modified via complex integrative stress circuitries

Intensity of anxiety is modified via complex integrative stress circuitries

Attenuated orexinergic signaling underlies depression-like responses induced by daytime light deficiency

Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care

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