Positive GABA modulator‐like effects of 1,1,1‐trichloroethane

Abstract

Despite the magnitude of the problem, our understanding of the neurochemical systems responsible for the abuse‐related behavioral effects of inhalants is lacking. The drug discrimination paradigm in animals has proven to be a valuable tool for understanding the neurotransmitter systems underlying the subjective effects of many drugs and may be a useful procedure for examining inhalants. Sixteen B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12,000 ppm of 1,1,1‐trichloroethane (TCE) vapor from air using a two‐lever, food reinforced, operant procedure. All 16 mice acquired the TCE vapor discrimination. TCE vapor substituted for itself with concentrations of 8000 ppm and greater producing full substitution. Injected doses of the benzodiazepine, midazolam, as well as the barbiturate, pentobarbital, resulted in substitution in most animals. However, the subunit selective benzodiazepine, zaleplon, did not substitute for TCE. The GABA reuptake inhibitor, tiagabine, the GABA transaminase inhibitor, vigabatrin, and the competitive NMDA receptor antagonist, GCS 19755 all failed to produce TCE‐like discriminative stimulus effects. These results are consistent with the hypothesis that the discriminative stimulus of TCE is the result of an indirect, but somewhat selective, positive modulation of GABAA receptor activity. Supported by NIDA grant RO1‐DA020553.