title: Hypocretin receptor 1 blockade preferentially reduces high effort responding for cocaine without promoting sleep.
abstract: Recent evidence suggests that blockade of the hypocretin receptor 1 may act as a useful pharmacotherapy for cocaine abuse. Here we investigated the extent to which various doses of a hypocretin receptor 1 antagonist, SB-334867, affect cocaine self-administration at varying doses of cocaine and across a range of effort requirements, and tested if these SB-334867 doses produce sedative effects. First, we trained animals to self-administer one of three doses of cocaine on a progressive ratio schedule, and then tested the effects of three doses of SB-334867. Responding for cocaine was then analyzed to segregate features of relatively high and low effort requirements across the progressive ratio session. In another set of experiments, we tested potential sleep-promoting effects of the same doses of SB-334867. Our data indicate that blockade of hypocretin receptor 1 preferentially reduces high effort responding for cocaine at levels that do not promote sedation.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Brodnik
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Bernstein
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Courtney D
authors.initials: CD
authors.lastname: Prince
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: respana@drexelmed.edu.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: España
mesh_terms: D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D001583:Benzoxazoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology*; D064446:Orexin Receptors / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D012890:Sleep / Q000187:drug effects*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D018765:Dopamine Uptake Inhibitors; C578627:Hcrtr1 protein, rat; D006993:Hypnotics and Sedatives; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D014508:Urea; D003042:Cocaine
keywords: Addiction; Drug abuse; EEG/EMG; Orexin; Progressive ratio; SB-334867