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EVALUATING THE NMDA-GLUTAMATE RECEPTOR AS A SITE OF ACTION FOR TOLUENE, IN VIVO
Citation:
BALE, A., M. D. JACKSON, Q. T. KRANTZ, V. A. BENIGNUS, P. J. BUSHNELL, T. J. SHAFER, AND W. K. BOYES. EVALUATING THE NMDA-GLUTAMATE RECEPTOR AS A SITE OF ACTION FOR TOLUENE, IN VIVO. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 98(1):159-166, (2007).
Impact/Purpose:
To help determine whether effects on NMDA receptors contribute to toluene-induced alterations in pattern-elicited VEPs
Description:
In vitro, toluene disrupts the function of NMDA-glutamate receptors, indicating that effects on NMDA receptor function may contribute to toluene neurotoxicity. NMDA-glutamate receptors are widely present in the visual system and contribute to pattern-elicited visual evoked potentials (VEPs) in rodents, a measure that is altered by toluene exposure. The present study tested the hypothesis that effects on NMDA receptors contribute to toluene-induced alterations in pattern-elicited VEPs. Long-Evans rats were exposed to toluene by inhalation and VEPs were measured during toluene exposure in the presence or absence of NMDA or MK-801. Pattern-elicited VEPs were collected by exposing rats to a sinusoidal pattern at a frequency of 4.55 Hz. Following collection of baseline VEPs, rats were injected with either saline, NMDA (2.5, 10 mg/kg, i.p.), or MK-801 (0.1, 0.33, 0.7 mg/kg, i.p.) and 10minutes later were exposed to air or toluene (2000 ppm). VEP amplitudes were calculated for 1X (F1) and 2X stimulus frequency (F2). The F2 amplitude was reduced by approximately 60, 60 and 50% in the toluene-exposed groups (TOL): SALINE/TOL(n=11), NMDA/TOL (2.5 mg/kg; n=13), and NMDA/TOL (10 mg/kg, n=11),respectively. Thus, NMDA (2.5 and 10 mg/kg) did not significantly affect toluenemediatedF2 amplitude effects. Administration of 0.1 mg/kg MK-801 prior to toluene exposure blocked the F2 amplitude decreases caused by toluene (n=9). However, when0.1 mg/kg MK-801 was administered 20 minutes after the onset of toluene exposure, toluene-mediated F2 amplitude decreases persisted despite the challenge by MK801.These data support the hypothesis that acute actions of toluene on pattern-elicited VEPs involve NMDA receptors