Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors
Cocaine and oxycodone use disorders represent urgent public health burdens, with limited treatment options for opioid dependence and no approved pharmacotherapies for cocaine-related disorders, highlighting the critical need to uncover novel molecular targets in the addiction neurocircuitry. The bas...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Addiction Neuroscience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772392525000276 |
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| author | Courtney P. Wood Arnav Gurha Caitlin Crook Angelica Martinez Selen Dirik Cloe Moreno Anirudh Vaiyapuri Avraham Libster Francesca Telese Giordano de Guglielmo |
| author_facet | Courtney P. Wood Arnav Gurha Caitlin Crook Angelica Martinez Selen Dirik Cloe Moreno Anirudh Vaiyapuri Avraham Libster Francesca Telese Giordano de Guglielmo |
| author_sort | Courtney P. Wood |
| collection | DOAJ |
| description | Cocaine and oxycodone use disorders represent urgent public health burdens, with limited treatment options for opioid dependence and no approved pharmacotherapies for cocaine-related disorders, highlighting the critical need to uncover novel molecular targets in the addiction neurocircuitry. The basolateral amygdala (BLA) modulates withdrawal and drug-seeking behaviors in substance use disorders (SUDs), but the molecular drivers of these effects are poorly understood. Here, we investigated the role of corticotrophin-releasing hormone binding protein (CRHBP) in the BLA using viral-mediated knockdown, single-nucleus RNA sequencing (snRNA-seq), and operant self-administration in rats. snRNA-seq revealed Crhbp expression in BLA somatostatin-positive interneurons, with minimal presence in the central amygdala. Crhbp knockdown in the BLA decreased cocaine self-administration and cue-induced reinstatement, suggesting a role in sustaining stimulant addiction. Conversely, it increased oxycodone intake and progressive ratio breakpoints, indicating heightened opioid reinforcement, while also elevating cue-induced reinstatement after 24 h of abstinence, reflecting enhanced opioid-seeking. These opposing effects highlight Crhbp’s substance-specific influence on addiction-related behaviors in the BLA. Our findings position Crhbp as a potential therapeutic target gene for tailored interventions in cocaine and opioid SUDs. |
| format | Article |
| id | doaj-art-60a2ecbd3cd945388c22d27f0fa2cc98 |
| institution | Kabale University |
| issn | 2772-3925 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Addiction Neuroscience |
| spelling | doaj-art-60a2ecbd3cd945388c22d27f0fa2cc982025-08-20T04:00:32ZengElsevierAddiction Neuroscience2772-39252025-09-011610022110.1016/j.addicn.2025.100221Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviorsCourtney P. Wood0Arnav Gurha1Caitlin Crook2Angelica Martinez3Selen Dirik4Cloe Moreno5Anirudh Vaiyapuri6Avraham Libster7Francesca Telese8Giordano de Guglielmo9Psychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA; School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino (MC), 62032, ItalyPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USAPsychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Corresponding authors.Psychiatry Department, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Corresponding authors.Cocaine and oxycodone use disorders represent urgent public health burdens, with limited treatment options for opioid dependence and no approved pharmacotherapies for cocaine-related disorders, highlighting the critical need to uncover novel molecular targets in the addiction neurocircuitry. The basolateral amygdala (BLA) modulates withdrawal and drug-seeking behaviors in substance use disorders (SUDs), but the molecular drivers of these effects are poorly understood. Here, we investigated the role of corticotrophin-releasing hormone binding protein (CRHBP) in the BLA using viral-mediated knockdown, single-nucleus RNA sequencing (snRNA-seq), and operant self-administration in rats. snRNA-seq revealed Crhbp expression in BLA somatostatin-positive interneurons, with minimal presence in the central amygdala. Crhbp knockdown in the BLA decreased cocaine self-administration and cue-induced reinstatement, suggesting a role in sustaining stimulant addiction. Conversely, it increased oxycodone intake and progressive ratio breakpoints, indicating heightened opioid reinforcement, while also elevating cue-induced reinstatement after 24 h of abstinence, reflecting enhanced opioid-seeking. These opposing effects highlight Crhbp’s substance-specific influence on addiction-related behaviors in the BLA. Our findings position Crhbp as a potential therapeutic target gene for tailored interventions in cocaine and opioid SUDs.http://www.sciencedirect.com/science/article/pii/S2772392525000276AmygdalaAddictionCocaineOxycodoneCorticotrophin-releasing binding protein |
| spellingShingle | Courtney P. Wood Arnav Gurha Caitlin Crook Angelica Martinez Selen Dirik Cloe Moreno Anirudh Vaiyapuri Avraham Libster Francesca Telese Giordano de Guglielmo Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors Addiction Neuroscience Amygdala Addiction Cocaine Oxycodone Corticotrophin-releasing binding protein |
| title | Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors |
| title_full | Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors |
| title_fullStr | Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors |
| title_full_unstemmed | Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors |
| title_short | Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors |
| title_sort | corticotrophin releasing hormone binding protein in the basolateral amygdala divergent roles in cocaine and opioid addiction like behaviors |
| topic | Amygdala Addiction Cocaine Oxycodone Corticotrophin-releasing binding protein |
| url | http://www.sciencedirect.com/science/article/pii/S2772392525000276 |
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