, Volume 231, Issue 7, pp 1339–1350 | Cite as

Assessment of reinforcement enhancing effects of toluene vapor and nitrous oxide in intracranial self-stimulation

  • Matthew E. Tracy
  • Galina G. Slavova-Hernandez
  • Keith L. SheltonEmail author
Original Investigation



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).


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.


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.


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.


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.


Rate-frequency ICSS Intracranial self-stimulation Mice Inhalant Toluene Nitrous oxide Diazepam Progressive ratio Cocaine 



This study is funded by National Institute of Drug Abuse grant no. R01DA-020553 and F31DA034469.

Conflict of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Matthew E. Tracy
    • 1
  • Galina G. Slavova-Hernandez
    • 1
  • Keith L. Shelton
    • 1
    Email author
  1. 1.Department of Pharmacology and ToxicologyVirginia Commonwealth University School of MedicineRichmondUSA

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