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 GABAA receptor positive modulatory effects.

Trichloroethylene poses health risks, US EPA confirms

“…Neuronal degeneration (Gash et al, 2008) and diminished sciatic nerve regeneration (Kjellstrand et al, 1987) were also observed following TCE exposure in rodents, however those studies scored Low and Unacceptable, respectively in data quality evaluation. More recent studies have observed both sedative (Wilmer et al, 2014) and stimulatory effects (Shelton and Nicholson, 2014) of TCE via inhalation at doses at or above 5000 ppm. Rats administered TCE via gavage for 6 weeks demonstrated loss of dopaminergic neurons at 500 and 1000 mg/kg-day, with changes in behavior and reduced mitochondrial activity with increased oxidative stress observed at 1000 mg/kg-day (Liu et al, 2010).…”