Inhaled toluene vapor as a discriminative stimulus

Few studies exist exploring the discriminative stimulus effects of inhalants and none that have trained an interoceptive discrimination using the inhaled route. This study was designed to assess if it was possible to train an inhaled toluene discrimination. The second objective was to determine whether the discrimination was based on interoceptive or exteroceptive stimulus effects. Eight B6SJLF1/J mice were trained to discriminate 10 min of exposure to 6000 ppm inhaled toluene vapor from air, using a standard food-reinforced operant procedure. Toluene vapor produced robust, concentration-dependent, discriminative stimulus effects, with concentrations of 4000 ppm and higher producing full substitution. Substitution of inhaled toluene vapor for the training condition was exposure-time dependent. A minimum of 7 min of exposure to 6000 ppm was required to produce complete substitution. Injected intraperitoneal toluene produced dose-dependent full substitution for inhaled toluene vapor. Both inhaled and intraperitoneal ethylbenzene produced similar levels of partial substitution for 6000 ppm toluene vapor. Inhaled isoflurane vapor produced no substitution for toluene vapor. These results show that a toluene vapor discrimination can be successfully trained in mice and the discrimination is selective for toluene compared to ethylbenzene and isoflurane. The results also suggest that the discrimination was likely to have been based primarily on interoceptive rather than exteroceptive stimulus effects.