CRF-5-HT interactions in the dorsal raphe nucleus and motivation for stress-induced opioid reinstatement

Li, Chen; McCloskey, Nicholas; Phillips, Jared; Simmons, Steven J.; Kirby, Lynn G.

doi:10.1007/s00213-020-05652-3

Cited by 11 publications

(4 citation statements)

References 88 publications

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“…Morphine CPP test. The CPP procedure was adapted from our previous rat models (Li et al, 2013(Li et al, , 2021. The CPP apparatus was a Plexiglas chamber (12.7 cm × 34.7 cm × 12.7 cm) that consisted of two identically sized compartments with a guillotine door (5 cm × 5.9 cm) in-between.…”

Section: Splash Testmentioning

confidence: 99%

Role of α1-GABA_A receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Li,

McElroy,

Phillips

et al. 2024

J Psychopharmacol

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Background: The serotonin (5-hydroxytryptamine (5-HT))-mediated system plays an important role in stress-related psychiatric disorders and substance abuse. Our previous studies showed that stress and drug exposure can modulate the dorsal raphe nucleus (DRN)-5-HT system via γ-aminobutyric acid (GABA)A receptors. Moreover, GABAA receptor-mediated inhibition of serotonergic DRN neurons is required for stress-induced reinstatement of opioid seeking. Aim/methods: To further test the role of GABAA receptors in the 5-HT system in stress and opioid-sensitive behaviors, our current study generated mice with conditional genetic deletions of the GABAA α1 subunit to manipulate GABAA receptors in either the DRN or the entire population of 5-HT neurons. The GABAA α1 subunit is a constituent of the most abundant GABAA subtype in the brain and the most highly expressed subunit in 5-HT DRN neurons. Results: Our results showed that mice with DRN-specific knockout of α1-GABAA receptors exhibited a normal phenotype in tests of anxiety- and depression-like behaviors as well as swim stress-induced reinstatement of morphine-conditioned place preference. By contrast, mice with 5-HT neuron-specific knockout of α1-GABAA receptors exhibited an anxiolytic phenotype at baseline and increased sensitivity to post-morphine withdrawal-induced anxiety. Conclusions: Our data suggest that GABAA receptors on 5-HT neurons contribute to anxiety-like behaviors and sensitivity of those behaviors to opioid withdrawal.

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Section: Splash Testmentioning

confidence: 99%

Role of α1-GABA_A receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Li,

McElroy,

Phillips

et al. 2024

J Psychopharmacol

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“…Stressors could inhibit 5-HT neuron activity by stimulating the release of CRH in DRN, which is mediated by CRHR1 located on GABA afferent neurons, whereas CRHR2 mediates an opposite effect, promoting the release of 5-HT. [56][57][58][59] Another study has shown that low-dose CRH binds to CRHR1 while high-dose CRH combines with CRHR2. 60 In addition, inhibition of DRN 5-HT by CRH may lead to visceral hyperalgesia, for the reason that 5-HT is also a main factor of central descending pain-inhibiting system, however, this response can be inhibited by lateral ventricular injection of CRHR1 antagonists or CRHR2 agonists.…”

Section: Dorsal Raphe Nucleusmentioning

confidence: 99%

Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders

et al. 2023

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Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.

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“…Interestingly, infusion of a CRF-R1 antagonist in the basolateral nucleus of the amygdala of rats can completely block the anxiety-like effects induced by CRF/CRF-R1 (Gehlert et al, 2005). In addition, research has shown that the negative emotional state induced by stressors can indirectly inhibit the activity of 5-HT neurons and the release of 5-HT by stimulating the release of CRF in the dorsal raphe nucleus (DRN) (Li, McCloskey, et al, 2021). This process is mediated by CRF-R1 located on GABAergic afferent fibers (Li, McCloskey, et al, 2021).…”

mentioning

confidence: 99%

“…In addition, research has shown that the negative emotional state induced by stressors can indirectly inhibit the activity of 5-HT neurons and the release of 5-HT by stimulating the release of CRF in the dorsal raphe nucleus (DRN) (Li, McCloskey, et al, 2021). This process is mediated by CRF-R1 located on GABAergic afferent fibers (Li, McCloskey, et al, 2021).…”

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confidence: 99%

Corticotropin‐releasing factor signaling and its potential role in the prefrontal cortex‐dependent regulation of anxiety

Yang,

Geng

2023

J of Neuroscience Research

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A large body of literature has highlighted the significance of the corticotropin‐releasing factor (CRF) system in the regulation of neuropsychiatric diseases. Anxiety disorders are among the most common neuropsychiatric disorders. An increasing number of studies have demonstrated that the CRF family mediates and regulates the development and maintenance of anxiety. Thus, the CRF family is considered to be a potential target for the treatment of anxiety disorders. The prefrontal cortex (PFC) plays a role in the occurrence and development of anxiety, and both CRF and CRF‐R1 are widely expressed in the PFC. This paper begins by reviewing CRF‐related signaling pathways and their different roles in anxiety and related processes. Then, the role of the CRF system in other neuropsychiatric diseases is reviewed and the potential role of PFC CRF signaling in the regulation of anxiety disorders is discussed. Although other signaling pathways are potentially involved in the process of anxiety, CRF in the PFC primarily modulates anxiety disorders through the activation of corticotropin‐releasing factor type1 receptors (CRF‐R1) and the excitation of the cAMP/PKA signaling pathway. Moreover, the main signaling pathways of CRF involved in sex differentiation in the PFC appear to be different. In summary, this review suggests that the CRF system in the PFC plays a critical role in the occurrence of anxiety. Thus, CRF signaling is of great significance as a potential target for the treatment of stress‐related disorders in the future.

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CRF-5-HT interactions in the dorsal raphe nucleus and motivation for stress-induced opioid reinstatement

Cited by 11 publications

References 88 publications

Role of α1-GABA_A receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Role of α1-GABA_A receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders

Corticotropin‐releasing factor signaling and its potential role in the prefrontal cortex‐dependent regulation of anxiety

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CRF-5-HT interactions in the dorsal raphe nucleus and motivation for stress-induced opioid reinstatement

Cited by 11 publications

References 88 publications

Role of α1-GABAA receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Role of α1-GABAA receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders

Corticotropin‐releasing factor signaling and its potential role in the prefrontal cortex‐dependent regulation of anxiety

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Product

Resources

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Role of α1-GABA_A receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression

Role of α1-GABA_A receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression