Characterization of an inhaled toluene drug discrimination in mice: Effect of exposure conditions and route of administration

Abstract

The drug discrimination procedure in animals has been extensively utilized to model the abuse related, subjective effects of drugs in humans, but it has seldom been used to examine abused volatile inhalants like toluene. The present study sought to characterize the temporal aspects of toluene's discriminative stimulus as well assess toluene blood concentrations under identical exposure conditions. B6SJLF1/J mice were trained to discriminate 10 min of exposure to 6000 ppm inhaled toluene vapor from air. Toluene vapor concentration dependently substituted for the training exposure condition with longer exposures to equivalent concentrations producing greater substitution than shorter exposures. Toluene's discriminative stimulus effects dissipated completely by 60 min after the cessation of exposure. Injected liquid toluene dose-dependently substituted for toluene vapor as well as augmenting the discriminative stimulus effects of inhaled toluene. Toluene blood concentrations measured under several exposure conditions which produced full substitution were all nearly identical suggesting that the concentration of toluene in the animals tissues at the time of testing determined discriminative performance. These results indicate that the discriminative stimulus effects of inhaled toluene vapor are likely mediated by CNS effects rather than by it's pronounced peripheral stimulus effects.

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

“…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).…”

Volatile Solvents as Drugs of Abuse: Focus on the Cortico-Mesolimbic Circuitry

“…Mice will fully discriminate vaporized toluene from air at concentrations between 4000 and 12000 p.p.m., and the discriminative time course mirrors the falling blood concentration after vapor concentration (Shelton and Slavova-Hernandez, 2009). Similarly, TCE can act as a discriminative stimulus, and other volatile solvents like toluene, ethylbenzene, o-xylene, TCY, and PERC all substitute for TCE (Shelton, 2009).…”

Adolescent toluene exposure produces enduring social and cognitive deficits in mice: An animal model of solvent-induced psychosis

“…This is hard to be conducted in animal models. Actually, intraperitoneal injection of toluene to rodents, like inhalation exposure, produced biphasic locomotor activity and stereotypic behaviours, which resemble behavioural signs observed in toluene abusers (Riegel and French 1999;Chan et al 2004) and full substitution for inhaled toluene in drug discrimination (Shelton and Slavova-Hernandez 2009). The concentration of toluene in the animal tissues at the time of testing determined the behavioural performance no matter the route of administration (Shelton and Slavova-Hernandez 2009).…”