Effects of inhaled toluene and 1,1,1-trichloroethane on seizures and death produced by N-methyl-D-aspartic acid in mice.

Abstract

Evidence exists that some abused solvents have N-methyl-D-aspartic acid (NMDA) antagonist activity, although which of their effects may be related to this mechanism is not well understood. The effects of toluene and 1,1,1-trichloroethane (TCE) on NMDA-induced seizures in mice were studied using three experimental protocols: (a) animals injected i.p. with 120 or 170 mg/kg NMDA and immediately afterwards exposed to solvent vapors or air for 30 min (co-exposure protocol); (b) mice exposed for 30 min to solvent or air, then injected with NMDA and placed in the chamber for a second 30-min exposure (pre-exposure+co-exposure protocol); and (c) mice that inhaled 4000 ppm toluene or air for 30 min twice a day, 6 h apart, for 7 days, and were injected with 120 mg/kg NMDA immediately before a 30-min toluene exposure (repeated exposure protocol). When given acutely, toluene, but not TCE, produced concentration-dependent protection against NMDA-induced seizures. Higher concentrations of toluene were also effective against the lethal effects produced by 170 mg/kg NMDA. Clearer effects were seen when the pre-exposure+co-exposure protocol was followed. Under these conditions the IC(50) for toluene was 739 ppm (653-825) against seizure occurrence and 2127 ppm (1966-2288) against lethality. Repeated exposure to toluene did not result in tolerance to its anticonvulsant effects. These results are consistent with the in vitro effects described for toluene as a noncompetitive NMDA antagonist and as a compound that enhances GABAergic transmission. The lack of protective effects of TCE is not consistent with its in vitro actions.

• Authors: Silvia Lorenia Cruz, Marcia Yvette Gauthereau, Cynthia Camacho-Muñoz, Carolina López-Rubalcava, Robert L Balster
• Journal: Behavioural brain research (Behav Brain Res) Vol. 140 Issue 1-2 Pg. 195-202 (Mar 18 2003) ISSN: 0166-4328 [Print] Netherlands
• PMID: 12644292 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticonvulsants
• Excitatory Amino Acid Agonists
• Illicit Drugs
• Solvents
• Trichloroethanes
• 1,1,1-trichloroethane
• Toluene
• N-Methylaspartate

Topics

• Animals
• Anticonvulsants (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Tolerance
• Excitatory Amino Acid Agonists (toxicity)
• Illicit Drugs (toxicity)
• Male
• Mice
• Mice, Inbred Strains
• N-Methylaspartate (toxicity)
• Seizures (chemically induced, drug therapy, mortality, physiopathology)
• Solvents (therapeutic use)
• Time Factors
• Toluene (therapeutic use)
• Trichloroethanes (therapeutic use)