Inhalant abuse poses a significant worldwide health problem, yet relatively little research has been conducted on the topic. A valuable research method for investigating drug addiction is the drug self-administration paradigm. Unfortunately, there is currently no small-animal model for studying self-administration of inhaled drugs. The proposed research will develop and evaluate a novel small-animal model of inhalant self-administration. Specifically, rats or mice will be placed inside a gas-tight cylinder with a maintained, linear concentration gradient of an abused drug, nitrous oxide. The gradient spans a range of nitrous oxide concentration from 0 to 60 percent. The animal is free to move along the length of the gradient and thereby select the concentration of nitrous oxide being inhaled (or the drug effect being experienced). The proposed research will evaluate this method and assess an experimental procedure that may facilitate the unambiguous interpretation of the subject's self-administration behavior. The proposed experiment will first determine whether rats will alter their selected location within the cylinder in association with the experimental manipulation of the polarity of the concentration gradient. The polarity of the concentration gradient will be changed four times within a single test session (i.e., an """"""""alternating gradient"""""""" paradigm). Individual rats will be given once-daily test sessions in the self-administration gradient over several weeks. Statistical analyses will evaluate the hypothesis that rats will increase their self-administration of nitrous oxide over repeated sessions. Additional analyses will be conducted to evaluate individual differences in nitrous oxide self-administration behavior. The rat inhalant self-administration apparatus will then be miniaturized for use with mice. As in the rat experiments, the """"""""alternating gradient"""""""" paradigm will be used to evaluate purposeful self-administration of nitrous oxide in mice. Developing this methodology will support our ongoing line of research investigating the role of individual differences in vulnerability to drug addiction and drug abuse. Furthermore, the development of this methodology for use with both rats and mice will provide a powerful research tool for investigators studying inhalant abuse.
| Ramsay, Douglas S; Watson, Chae H; Leroux, Brian G et al. (2003) Conditioned place aversion and self-administration of nitrous oxide in rats. Pharmacol Biochem Behav 74:623-33 |
