{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pantazis CB"],"funding":["NIDA NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse"],"pagination":["741-751"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8782853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["47(3)"],"pubmed_abstract":["Drug-associated sensory cues increase motivation for drug and the orexin system is importantly involved in this stimulus-enhanced motivation. Ventral tegmental area (VTA) is a major target by which orexin signaling modulates reward behaviors, but it is unknown whether this circuit is necessary for cue-driven motivation for cocaine. Here, we investigated the role of VTA orexin signaling in cue-driven motivation for cocaine using a behavioral economics (BE) paradigm. We found that infusion of the orexin-1 receptor (Ox1R) antagonist SB-334867 (SB) into VTA prior to BE testing reduced motivation when animals were trained to self-administer cocaine with discrete cues and tested on BE with those cues. SB had no effect when animals were trained to self-administer cocaine without cues or tested on BE without cues, indicating that learning to associate cues with drug delivery during self-administration training was necessary for cues to recruit orexin signaling in VTA. These effects were specific to VTA, as injections of SB immediately dorsal had no effect. Moreover, intra-VTA SB did not have an impact on locomotor activity, or low- or high-effort consumption of sucrose. Finally, we microinjected a novel retrograde adeno-associated virus (AAVretro) containing an orexin-specific short hairpin RNA (OxshRNA) into VTA to knock down orexin in the hypothalamus-VTA circuit. These injections significantly reduced orexin expression in lateral hypothalamus (LH) and decreased cue-driven motivation. These studies demonstrate a role for orexin signaling in VTA, specifically when cues predict drug reward."],"journal":["Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology"],"pubmed_title":["Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine."],"pmcid":["PMC8782853"],"funding_grant_id":["F31 DA042588","R01DA006214","K99DA045765","R01 DA006214","F31DA042588","R00 DA045765"],"pubmed_authors":["James MH","Shin N","Pantazis CB","O'Connor S","Aston-Jones G"],"additional_accession":[]},"is_claimable":false,"name":"Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine.","description":"Drug-associated sensory cues increase motivation for drug and the orexin system is importantly involved in this stimulus-enhanced motivation. Ventral tegmental area (VTA) is a major target by which orexin signaling modulates reward behaviors, but it is unknown whether this circuit is necessary for cue-driven motivation for cocaine. Here, we investigated the role of VTA orexin signaling in cue-driven motivation for cocaine using a behavioral economics (BE) paradigm. We found that infusion of the orexin-1 receptor (Ox1R) antagonist SB-334867 (SB) into VTA prior to BE testing reduced motivation when animals were trained to self-administer cocaine with discrete cues and tested on BE with those cues. SB had no effect when animals were trained to self-administer cocaine without cues or tested on BE without cues, indicating that learning to associate cues with drug delivery during self-administration training was necessary for cues to recruit orexin signaling in VTA. These effects were specific to VTA, as injections of SB immediately dorsal had no effect. Moreover, intra-VTA SB did not have an impact on locomotor activity, or low- or high-effort consumption of sucrose. Finally, we microinjected a novel retrograde adeno-associated virus (AAVretro) containing an orexin-specific short hairpin RNA (OxshRNA) into VTA to knock down orexin in the hypothalamus-VTA circuit. These injections significantly reduced orexin expression in lateral hypothalamus (LH) and decreased cue-driven motivation. These studies demonstrate a role for orexin signaling in VTA, specifically when cues predict drug reward.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2025-04-19T17:57:38.09Z","creation":"2025-04-19T17:57:38.09Z"},"accession":"S-EPMC8782853","cross_references":{"pubmed":["34635803"],"doi":["10.1038/s41386-021-01173-5"]}}