Pharmacological classification of the abuse-related discriminative stimulus effects of trichloroethylene vapor

Abstract

Inhalants are distinguished as a class primarily based upon a shared route of administration. Grouping inhalants according to their abuse-related in vivo pharmacological effects using the drug discrimination procedure has the potential to provide a more relevant classification scheme to the research and treatment community. Mice were trained to differentiate the introceptive effects of the trichloroethylene vapor from air using an operant procedure. Trichloroethylene is a chlorinated hydrocarbon solvent once used as an anesthetic as well as in glues and other consumer products. It is now primarily employed as a metal degreaser. We found that the stimulus effects of trichloroethylene were similar to those of other chlorinated hydrocarbon vapors, the aromatic hydrocarbon toluene and the vapor anesthetics methoxyflurane and isoflurane. The stimulus effects of trichloroethylene overlapped with those of the barbiturate methohexital, to a lesser extent the benzodiazepine midazolam and to ethanol. NMDA antagonists, the kappa opioid agonist U50,488 and the mixed 5-HT agonist mCPP largely failed to substitute for trichloroethylene. These data suggest that stimulus effects of chlorinated hydrocarbon vapors are mediated at least partially by GABA_A receptor positive modulatory effects.

Fig. 1

Upper panel shows percentage trichloroethylene-lever selection (±SEM) for tests sessions conducted after exposure to 1, 2, 3, 7 or 10 min of 6000 ppm trichloroethylene vapor. Lower panel shows trichloroethylene-lever selection (±SEM) resulting from delaying the start of the test session for 0, 3, 10, 30 or 60 min after cessation of exposure to 10 min of 6000 ppm trichloroethylene vapor.

Fig. 2

Mean percentage trichloroethylene-lever selection (±SEM) following 10 min of exposure to increasing concentrations of trichloroethylene (blue squares), 1,1,1-trichloroethane (red circles) or tetrachloroethylene (green triangles) in mice trained to discriminate 6000 ppm inhaled trichloroethylene vapor from air. Points above Air (closed symbols) and TRI (open symbols) represent the results of air and 6000 ppm inhaled trichloroethylene exposure control sessions.

Fig. 3

Mean percentage trichloroethylene-lever selection (±SEM) following 10 min of exposure to increasing concentration of toluene (blue squares), isoflurane (red circles) or methoxyflurane (green triangles) in mice trained to discriminate 6000 ppm inhaled trichloroethylene vapor from air. Points above Air (filled symbols) and TRI (open symbols) represent the results of air and 6000 ppm inhaled trichloroethylene exposure control sessions.

Fig. 4

Dose-effect curves for midazolam (blue squares), methohexital (red circles), [+]MK-801 (green triangles), CGS-19755 (purple diamonds) and ethanol (black inverted triangles) in mice trained to discriminate 6000 ppm inhaled trichloroethylene vapor from air. Points above Air (filled symbols) and TRI (open symbols) represent the results of air and 6000 ppm inhaled trichloroethylene exposure control sessions. Mean (± SEM) percentages trichloroethylene-lever responding are shown in the upper panel, mean (± SEM) response rates in responses/sec are shown in the bottom panel.