title: Assessment of reinforcement enhancing effects of toluene vapor and nitrous oxide in intracranial self-stimulation.
abstract: BACKGROUND
  Despite widespread abuse, there are few validated methods to study the rewarding effects of inhalants. One model that may have utility for this purpose is intracranial self-stimulation (ICSS).
  
  
  OBJECTIVE
  This study aims to compare and contrast the ICSS reward-facilitating effects of abused inhalants to other classes of abused drugs. Compounds were examined using two different ICSS procedures in mice to determine the generality of each drug's effects on ICSS and the sensitivity of the procedures.
  
  
  METHODS
  Male C57BL/6J mice with electrodes implanted in the medial forebrain bundle were trained under a three-component rate-frequency as well as a progressive ratio (PR) ICSS procedure. The effects of nitrous oxide, toluene vapor, cocaine, and diazepam on ICSS were then examined.
  
  
  RESULTS
  Concentrations of 1,360-2,900 parts per million (ppm) inhaled toluene vapor significantly facilitated ICSS in the rate-frequency procedure and 1,360 ppm increased PR breakpoint. A concentration of 40 % nitrous oxide facilitated ICSS in the rate-frequency procedure but reduced PR breakpoint. Doses of 3-18 mg/kg cocaine facilitated ICSS in the rate-frequency procedure, and 10 and 18 mg/kg increased PR breakpoint. Doses of 1 and 3 mg/kg diazepam facilitated ICSS in the rate-frequency procedure, and 3 mg/kg increased PR breakpoint.
  
  
  CONCLUSIONS
  The reinforcement-facilitating effect of toluene in ICSS is at least as great as diazepam. By contrast, nitrous oxide weakly enhances ICSS in only the rate-frequency procedure. The data suggest that the rate-frequency procedure may be more sensitive than the PR schedule to the reward-facilitating effects of abused inhalants.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, 410 North 12th Street, Room 746D, Richmond, VA, 23298-0613, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Tracy
authors.forename: Galina G
authors.initials: GG
authors.lastname: Slavova-Hernandez
authors.forename: Keith L
authors.initials: KL
authors.lastname: Shelton
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005740:Gases / Q000008:administration & dosage / Q000494:pharmacology; D013287:Illicit Drugs / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012201:Reward; D012653:Self Stimulation; D014050:Toluene / Q000008:administration & dosage / Q000494:pharmacology*; D014835:Volatilization
chemical_list: D005740:Gases; D013287:Illicit Drugs; D014050:Toluene; D003042:Cocaine; D009609:Nitrous Oxide; D003975:Diazepam