Inhaled toluene vapor as a discriminative stimulus

Abstract

Objectives-There have been few studies 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.Methods-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.Results-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 i.p. toluene produced dose-dependent full substitution for inhaled toluene vapor. Both inhaled and i.p. ethylbenzene produced similar levels of partial substitution for 6000 ppm toluene vapor. Inhaled isoflurane vapor produced no substitution for toluene vapor.Conclusions-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.

The group II metabotropic glutamate receptor agonist LY379268 reduces toluene-induced enhancement of brain-stimulation reward and behavioral disturbances

“…Actually, it has been reported that 560 mg/kg i.p. toluene produced 99% toluene vapor-lever responding for the 10 min 6000 ppm toluene vapor training condition in drug discrimination studies (Shelton 2007; Shelton and Slavova-Hernandez 2009). In addition, the toluene blood concentrations measured under several exposure conditions which produced full substitution were all nearly identical (Shelton and Slavova-Hernandez, 2009).…”

Pharmacological Characterization of the Discriminative Stimulus of Inhaled 1,1,1-Trichloroethane

“…Closed-loop recirculation of chamber atmosphere through a Miran 1A single-wavelength infrared spectrophotometer (Foxboro Co., Sharon, MA) indicated that TCE vapor concentration in the chambers reached equilibrium in less than 1 min for all tested concentrations (see Shelton, 2007 for more details of this procedure).…”

“…The static vapor chambers and general procedures used to expose the mice to TCE vapor before drug discrimination testing have been described previously (Shelton, 2007). Closed-loop recirculation of chamber atmosphere through a Miran 1A single-wavelength infrared spectrophotometer (Foxboro Co., Sharon, MA) indicated that TCE vapor concentration in the chambers reached equilibrium in less than 1 min for all tested concentrations (see Shelton, 2007 for more details of this procedure).…”

“…These mice were supplemented with an additional 12 adult male B6SJLF1/J mice used only for TCE blood concentration analysis. The B6SJLF1/J strain has been used extensively in my laboratory for drug discrimination studies with TCE and toluene vapor providing knowledge of appropriate test conditions (Shelton, 2007(Shelton, , 2009Shelton and Slavova-Hernandez, 2009). The mice were individually housed on a 12-h light/dark cycle (lights on 7:00 AM).…”

Review of Toluene Actions: Clinical Evidence, Animal Studies, and Molecular Targets

“…self-administration [25] and intracranial self-stimulation [26]. Inhaled toluene acts as a robust discriminative stimulus [27, 28] and also produces CNS depressant-like [29–31] amphetamine-like [32] and PCP-like discriminative effects [33]. Similar to other CNS depressant drugs, toluene has anxiolytic-like properties [34–36], anticonvulsant effects [37–41] and impairs locomotor coordination [42, 43].…”