Increases in amphetamine-like discriminative stimulus effects of the abused inhalant toluene in mice

Toluene, an abused solvent, shares behavioral and pharmacological effects with abused depressant drugs. These effects include ethanol- and pentobarbital-like discriminative stimulus effects. There is also emerging evidence that this abused inhalant may share stimulus effects with abused central nervous system (CNS) stimulants. To further explore the discriminative stimulus effects of one abused inhalant, this experiment evaluated the amphetamine-like discriminative stimulus effects of toluene. Mice were trained to discriminate between d-amphetamine (1.0 mg/kg) and saline in a two-lever drug discrimination procedure in which responding was under the control of a fixed-ratio 15 schedule. Mice were tested after 10-min inhalation exposures to air or toluene (500-6,000 ppm) and stimulus generalization was examined at 0, 15, 30, 45, 60, and 75 min post-exposure. Concentration-related increases in amphetamine-lever responding were observed for amphetamine doses > 0.56 mg/kg with full substitution occurring immediately after testing for 1.0 and 1.78 mg/kg. Partial amphetamine-lever responding was observed for all concentrations of toluene across the 75-min post-exposure test trials. Response rates that had decreased immediately after all toluene exposures recovered within 15-min post exposure. This partial substitution of toluene for amphetamine suggests that studies of the effects of abused solvents on brain dopaminergic systems need to be included in the study of possible CNS mechanisms.