Reviewing the role of the orexinergic system and stressors in modulating mood and reward-related behaviors

Vaseghi, Salar; Zarrabian, Shahram; Haghparast, Abbas

doi:10.1016/j.neubiorev.2021.104516

Cited by 19 publications

(7 citation statements)

References 265 publications

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“…OX 1 receptor signaling in the lateral paragigantocellularis ( Rezaei et al, 2020 ) and dorsal hippocampus ( Hooshmandi et al, 2017a ) has also been associated with the expression of opioid withdrawal. OX receptor signaling in the dorsal hippocampus has also been shown to be involved in the acquisition, expression, and reinstatement of morphine-induced CPP ( Guo et al, 2015 ; Sadeghi et al, 2016 ; Alizamini et al, 2018 ; Farahimanesh et al, 2018 ; also see Zarrabian et al, 2020 ; Vaseghi et al, 2022 ). These findings suggest that OX system activities throughout a wide system of brain regions contribute to the expression of behaviors related to opioid taking and seeking.…”

Section: Discussionmentioning

confidence: 99%

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

et al. 2023

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Background: The Department of Health and Human Services reports that prescription pain reliever (e.g., oxycodone) misuse was initiated by 4,400 Americans each day in 2019. Amid the opioid crisis, effective strategies to prevent and treat prescription opioid use disorder (OUD) are pressing. In preclinical models, the orexin system is recruited by drugs of abuse, and blockade of orexin receptors (OX receptors) prevents drug-seeking behavior. The present study sought to determine whether repurposing suvorexant (SUV), a dual OX receptor antagonist marketed for the treatment of insomnia, can treat two features of prescription OUD: exaggerated consumption and relapse.Methods: Male and female Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i. v., 8 h/day) in the presence of a contextual/discriminative stimulus (SD) and the ability of SUV (0–20 mg/kg, p. o.) to decrease oxycodone self-administration was tested. After self-administration testing, the rats underwent extinction training, after which we tested the ability of SUV (0 and 20 mg/kg, p. o.) to prevent reinstatement of oxycodone seeking elicited by the SD.Results: The rats acquired oxycodone self-administration and intake was correlated with the signs of physical opioid withdrawal. Additionally, females self-administered approximately twice as much oxycodone as males. Although SUV had no overall effect on oxycodone self-administration, scrutiny of the 8-h time-course revealed that 20 mg/kg SUV decreased oxycodone self-administration during the first hour in males and females. The oxycodone SD elicited strong reinstatement of oxycodone-seeking behavior that was significantly more robust in females. Suvorexant blocked oxycodone seeking in males and reduced it in females.Conclusions: These results support the targeting of OX receptors for the treatment for prescription OUD and repurposing SUV as pharmacotherapy for OUD.

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Section: Discussionmentioning

confidence: 99%

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

et al. 2023

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“…Prior studies have provided evidence supporting the crucial role of LH orexinergic neurons in the regulation of anxiodepression [ 24 ]. RS is one of the stressors in UCMS, often employed as a singular stressor to induce anxiety- and depression-like behaviors [ 15 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair

Liu,

Zheng,

Hui

et al. 2024

Transl Psychiatry

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Chronic stress-induced anxiodepression is a common health problem, however its potential neurocircuitry mechanism remains unclear. We used behavioral, patch-clamp electrophysiology, chemogenetic, and optogenetic approaches to clarify the response of the lateral hypothalamus (LH) and the medial prefrontal cortex (mPFC) to stress, confirmed the structural connections between the LH and mPFC, and investigated the role of the LH–mPFC pathway in chronic stress-induced anxiodepression symptoms. Unpredictable chronic mild stress (UCMS) caused anxiodepression-like behaviors, including anxiety, anhedonia, and despair behaviors. We discovered that the activity of the LH and mPFC was both increased after restraint stress (RS), a stressor of UCMS. Then we found that the orexinergic neurons in the LH predominantly project to the glutamatergic neurons in the mPFC, and the excitability of these neurons were increased after UCMS. In addition, overactivated LH orexinergic terminals in the mPFC induced anhedonia but not anxiety and despair behaviors in naive mice. Moreover, chemogenetically inhibited LH–mPFC orexinergic projection neurons and blocked the orexin receptors in the mPFC alleviated anhedonia but not anxiety and despair behaviors in UCMS-treated mice. Our study identified a new neurocircuit from LH orexinergic neurons to mPFC and revealed its role in regulating anhedonia in response to stress.

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“…The hypocretin system consists of two neuropeptides, the 33-amino acid Orexin-A (OrxA = Hcrt-1) and the 28-amino acid Orexin-B (OrxB = Hcrt-2), and two types of receptors, the HCRT-R1 and the HCRT-R2. Hypocretins are involved in the regulation of arousal, homeostasis, and circadian rhythms, which if dysregulated lead to daytime drowsiness and even narcolepsy [ 268 , 269 , 270 , 271 ]. Orexin type 1 receptors have been associated with the promotion of anxiety and depressive-like behavior, while the type 2 receptors exhibit anxiolytic and antidepressant effects [ 272 ].…”

Section: Neuropeptides In Anxiety and Depressionmentioning

confidence: 99%

“…More recently, a contradictory finding was reported in an animal study, in which intracerebral application of an orexin receptor agonist resulted in a reduction of anxious and depressive behaviors, whilst its antagonists induced anxious and depressive behavior [ 268 ]. The latest reviews suggest different roles of orexins in anxiety and depression, concluding that orexins are anxiogenic, while they also probably play a role in depression, but this role is to be further elucidated [ 271 , 276 ].…”

Section: Neuropeptides In Anxiety and Depressionmentioning

confidence: 99%

Anxiety and Depression: What Do We Know of Neuropeptides?

Kupcová

Danišovič

Grgac

et al. 2022

Behavioral Sciences

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In modern society, there has been a rising trend of depression and anxiety. This trend heavily impacts the population’s mental health and thus contributes significantly to morbidity and, in the worst case, to suicides. Modern medicine, with many antidepressants and anxiolytics at hand, is still unable to achieve remission in many patients. The pathophysiology of depression and anxiety is still only marginally understood, which encouraged researchers to focus on neuropeptides, as they are a vast group of signaling molecules in the nervous system. Neuropeptides are involved in the regulation of many physiological functions. Some act as neuromodulators and are often co-released with neurotransmitters that allow for reciprocal communication between the brain and the body. Most studied in the past were the antidepressant and anxiolytic effects of oxytocin, vasopressin or neuropeptide Y and S, or Substance P. However, in recent years, more and more novel neuropeptides have been added to the list, with implications for the research and development of new targets, diagnostic elements, and even therapies to treat anxiety and depressive disorders. In this review, we take a close look at all currently studied neuropeptides, their related pathways, their roles in stress adaptation, and the etiology of anxiety and depression in humans and animal models. We will focus on the latest research and information regarding these associated neuropeptides and thus picture their potential uses in the future.

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Reviewing the role of the orexinergic system and stressors in modulating mood and reward-related behaviors

Cited by 19 publications

References 265 publications

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair

Anxiety and Depression: What Do We Know of Neuropeptides?

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