Orexins and stress

Grafe, Laura A.; Bhatnagar, Seema

doi:10.1016/j.yfrne.2018.06.003

Cited by 94 publications

(77 citation statements)

References 210 publications

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“…Nonetheless, we found no evidence to support the possibility that the onset of puberty particularly increases vulnerability to PTSS development in females. Measurement of hormones, such as estrogen and orexin, which have been implicated in symptom development, could yield different conclusions (Grafe and Bhatnagar, 2018). Other factors may also explain sex differences in PTSS.…”

Section: Discussionmentioning

confidence: 99%

The emergence of sex differences in PTSD symptoms across development: evidence from the ALSPAC cohort

Haag

Fraser²,

Hiller

et al. 2019

Psychol. Med.

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BackgroundCross-sectional evidence suggests females in late adolescence exhibit higher rates of post-traumatic stress symptoms (PTSS) than males and younger age groups. However, longitudinal evidence is limited, and underlying factors are not well understood. We investigated the emergence of sex differences in PTSS from childhood to adolescence in a large, longitudinal UK cohort, and tested whether these could be explained by overlap between PTSS and depressive symptoms, or onset of puberty.MethodsTrauma exposure and PTSS were assessed at ages 8, 10, 13 (parent-report) and 15 (self-report) years in a sub-sample of 9966 children and adolescents from the ALSPAC cohort-study. Analyses of PTSS focused on those who reported potential trauma-exposure at each time-point (ranged fromn= 654 at 15 years ton= 1231 at 10 years). Age at peak-height velocity (APHV) was used as an indicator of pubertal timing.ResultsThere was no evidence of sex differences in PTSS at ages 8 and 10, but females were more likely to show PTSS at ages 13 (OR 1.54,p= 0.002) and 15 (OR 2.04,p= .001), even once symptoms related to depression were excluded. We found little evidence that the emergence of sex differences was related to pubertal timing (as indexed by APHV).ConclusionsResults indicate that females show higher levels of PTSS in adolescence but not during childhood. The emergence of this sex difference does not seem to be explained by overlap with depressive symptoms, while the influence of pubertal status requires further investigation.

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Section: Discussionmentioning

confidence: 99%

The emergence of sex differences in PTSD symptoms across development: evidence from the ALSPAC cohort

Haag

Fraser²,

Hiller

et al. 2019

Psychol. Med.

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“…Ultimately, it is important to better understand how sex and stress can influence structural differences, and thereby, functional differences in the orexin system. As the orexins display sex differences in expression and action (Grafe et al, 2017;Jöhren, 2018), potentiate the stress response (Kuru et al, 2000;von der Goltz et al, 2011), and are altered in psychiatric disorders (James et al, 2017;Grafe and Bhatnagar, 2018), this peptidergic system may be an important biological substrate in contributing to sex differences in stress-related mental illness. Figure 1.…”

Section: Discussionmentioning

confidence: 99%

“…Important changes in the cellular response, including decreases in neuronal firing rate, postsynaptic current, and reduction in neurotransmitter release, underlie these behavioral and physiological responses (Thompson and Spencer, 1966;Groves and Thompson, 1970;Castellucci and Kandel, 1974;Glanzman, 2006). Whether habituation takes place is dependent on the type, intensity, and duration of the stressor (Grafe and Bhatnagar, 2018). Typically, unpredictable chronic mild stress prevents habituation through variation in the type of stressor (Herman, 2013).…”

Section: Introductionmentioning

confidence: 99%

Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons

et al. 2019

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We recently found that non-stressed female rats have higher basal prepro-orexin expression and activation of orexinergic neurons compared to non-stressed males, which leads to impaired habituation to repeated restraint stress at the behavioral, neural, and endocrine level. Here, we extended our study of sex differences in the orexin system by examining spine densities and dendritic morphology in putative orexin neurons in adult male and female rats that were exposed to 5 consecutive days of 30 min restraint. Analysis of spine distribution and density indicated that putative orexinergic neurons in control non-stressed females had significantly more dendritic spines than those in control males, and the majority of these were mushroom spines. This morphological finding may suggest more excitatory input onto orexin neurons in female rats. As orexin neurons are known to promote the HPA response, this morphological change in orexin neurons could underlie the impaired habituation to repeated stress in female rats. Dendritic complexity did not differ between non-stressed males and females, however repeated restraint stress decreased total dendritic length, nodes, and branching primarily in males. Thus, reduced dendritic complexity of putative orexinergic neurons is observed in males but not in females after 5 days of repeated restraint stress. This morphological change might be reflective of decreased orexin system function, which may allow males to habituate more fully to repeated restraint than females.These results extend our understanding of the role of orexin neurons in regulating habituation and demonstrate changes in putative orexin cell morphology and spines that may underlie sex differences in habituation.

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“…Although Hcrt is exclusively produced in the LH, DMH, and PFA (Baldo et al, ; DiLeone et al, ; Winsky‐Sommerer et al, ), Hcrt neurons project widely throughout the brain (Peyron et al, ) and densely innervate such brain regions as the paraventricular nucleus of the thalamus (PVT), nucleus accumbens shell (NACsh), ventral pallidum (VP), VTA, CeA, BNST, and mPFC (Fig. ) , all of which are associated with arousal, motivation, and responses to stress and anxiety (e.g., Baldo et al, ; Peyron et al, , and for an extensive review, see Grafe and Bhatnagar, ). The anxiolytic effects of Hcrt‐r1 blockade, for example, were associated with a decrease in neural activity in both the BNST and CeA (Johnson et al, a,b) .…”

Section: Hcrt and Stressmentioning

confidence: 99%

Possible Role of CRF‐Hcrt Interaction in the Infralimbic Cortex in the Emergence and Maintenance of Compulsive Alcohol‐Seeking Behavior

Kim

Martin‐Fardon

2020

Alcoholism Clin & Exp Res

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Alcohol use disorder (AUD) is a chronic, relapsing disorder that is characterized by the compulsive use of alcohol despite numerous health, social, and economic consequences. Initially, the use of alcohol is driven by positive reinforcement. Over time, however, alcohol use can take on a compulsive quality that is driven by the desire to avoid the negative consequences of abstinence, including negative affect and heightened stress/anxiety. This transition from positive reinforcement-to negative reinforcement-driven consumption involves the corticotropin-releasing factor (CRF) system, although mounting evidence now suggests that the CRF system interacts with other neural systems to ultimately produce behaviors that are symptomatic of compulsive alcohol use, such as the hypocretin (Hcrt) system. Hypocretins are produced exclusively in the hypothalamus, but Hcrt neurons project widely throughout the brain and reach regions that perform regulatory functions for numerous behavioral and physiological responses-including the infralimbic cortex (IL) of the medial prefrontal cortex (mPFC). Although the entire mPFC undergoes neuroadaptive changes following prolonged alcohol exposure, the IL appears to undergo more robust changes compared with other mPFC substructures. Evidence to date suggests that the IL is likely involved in EtOH-seeking behavior, but ambiguities with respect to the specific role of the IL in this regard make it difficult to draw definitive conclusions. Furthermore, the manner in which CRF interacts with Hcrt in this region as it pertains to alcohol-seeking behavior is largely unknown, although immunohistochemical and electrophysiological experiments have shown that CRF and Hcrt directly interact in the mPFC, suggesting that the interaction between CRF and Hcrt in the IL may be critically important for the development and subsequent maintenance of compulsive alcohol seeking. This review aims to consolidate recent literature regarding the role of the IL in alcoholseeking behavior and to discuss evidence that supports a functional interaction between Hcrt and CRF in the IL.

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Orexins and stress

Cited by 94 publications

References 210 publications

The emergence of sex differences in PTSD symptoms across development: evidence from the ALSPAC cohort

The emergence of sex differences in PTSD symptoms across development: evidence from the ALSPAC cohort

Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons

Possible Role of CRF‐Hcrt Interaction in the Infralimbic Cortex in the Emergence and Maintenance of Compulsive Alcohol‐Seeking Behavior

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