title: Long-term cocaine self-administration under fixed-ratio and second-order schedules in monkeys.
abstract: BACKGROUND
  Studies in rodents have demonstrated that increased access to cocaine can result in increases in drug intake per unit time.
  
  
  OBJECTIVE
  The present studies characterized long-term changes in cocaine self-administration associated with quantitatively and qualitatively different conditions of cocaine availability in monkeys.
  
  
  METHODS
  Separate groups of rhesus monkeys (n = 6/group) self-administered cocaine (0.2 mg/kg per injection) under a fixed ratio (FR) 30 schedule for 3 h twice daily for two consecutive days each week for 1 year, or responded under a second-order FR 10 (fixed interval 3-min:S) schedule of 0.2 mg/kg per injection cocaine during daily sessions. After 18 weeks, probe sessions were conducted once per week, in which responding was maintained under a fixed interval (FI) 30-min schedule in the presence of distinct stimuli.
  
  
  RESULTS
  Weekly cocaine intakes under the FR schedule were stable in three subjects, but increased progressively in three monkeys over 1 year. In contrast, response rates under the second-order schedule were low and stable over time. Responding under the FI 30-min schedule was higher for monkeys in the FR group and pattern of responding was not indicative of FI performance, perhaps due to experimental history.
  
  
  CONCLUSIONS
  These data suggest that increases in cocaine intake can be observed under ratio schedules in monkeys. The use of an FI 30-min "probe" to assess changes in "drug seeking" appeared to be influenced by experimental history. These data may aid in the development of behavioral models of cocaine abuse, which focus on the compulsive nature of drug taking.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, 546 NRC, Winston-Salem, NC 27157-1083, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
authors.forename: Beth A
authors.initials: BA
authors.lastname: Reboussin
authors.forename: Tonya L
authors.initials: TL
authors.lastname: Calhoun
authors.forename: Susan H
authors.initials: SH
authors.lastname: Nader
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine