Evaluation of toluene dependence and cross-sensitization to diazepam

Acute effects of the abused inhalant toluene resemble those of CNS depressant drugs. Since abuse of toluene involves repeated use, the purpose of the present study was to evaluate the effects of repeated or continuous exposure to toluene and to compare these effects to those of other inhalants and depressants. In experiment 1, ICR mice exposed continuously to 250 ppm toluene via inhalation for four days developed mild dependence upon termination that was characterized by an increase in severity of handling-induced convulsions. However, administration of the convulsants, N-methyl-D-aspartate (NMDA) or pentylenetetrazole (PTZ), did not differentially affect toluene- vs. air-exposed mice. In experiment 2, CFW mice (but not ICR mice) developed cross-sensitization to the initial locomotor stimulatory effects of toluene following four days of injections with 10 mg/kg/day diazepam. Previous findings have shown that 1,1,1-trichloroethane (TCE) produced robust dependence and cross-sensitization to diazepam's locomotor effects when tested under similar conditions. The present results suggest that the dependence and cross-sensitization with diazepam produced by toluene are milder than those induced by TCE. Further, these studies add to increasing evidence that abused inhalants do not have identical pharmacological effects.