Amy R Johnson1, Matthew L Banks1, Bruce E Blough2, Joshua A Lile3, Katherine L Nicholson1, S Stevens Negus4. 1. Department of Pharmacology and Toxicology, Virginia Commonwealth University Richmond, VA, United States. 2. Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, NC, United States. 3. Departments of Behavioral Science, Psychiatry, and Psychology, University of Kentucky, Lexington, KY, United States. 4. Department of Pharmacology and Toxicology, Virginia Commonwealth University Richmond, VA, United States. Electronic address: sidney.negus@vcuhealth.org.
Abstract
BACKGROUND: Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. METHODS: Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. RESULTS: Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32-3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. CONCLUSIONS: These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder.
BACKGROUND: Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. METHODS: Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. RESULTS: Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32-3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. CONCLUSIONS: These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder.
Authors: E Andrew Townsend; S Stevens Negus; S Barak Caine; Morgane Thomsen; Matthew L Banks Journal: Neuropsychopharmacology Date: 2019-02-28 Impact factor: 7.853
Authors: Morgane Thomsen; Andrew C Barrett; Paul Butler; S Stevens Negus; S Barak Caine Journal: J Pharmacol Exp Ther Date: 2017-05-04 Impact factor: 4.030
Authors: Joshua A Lile; Amy R Johnson; Matthew L Banks; Kevin W Hatton; Lon R Hays; Katherine L Nicholson; Justin L Poklis; Abner O Rayapati; Craig R Rush; William W Stoops; S Stevens Negus Journal: Exp Clin Psychopharmacol Date: 2019-07-01 Impact factor: 3.157
Authors: Joshua A Lile; William W Stoops; Craig R Rush; S Stevens Negus; Paul E A Glaser; Kevin W Hatton; Lon R Hays Journal: Drug Alcohol Depend Date: 2016-05-28 Impact factor: 4.492