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EVALUATING MOLECULAR SITES OF ACTION FOR TOLUENE USING AN IN VIVO MODEL.
Citation:
Bale, A. S., Q T. Krantz, P J. Bushnell, T J. Shafer, AND W K. Boyes. EVALUATING MOLECULAR SITES OF ACTION FOR TOLUENE USING AN IN VIVO MODEL. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
In vitro studies have demonstrated that toluene disrupts the function of several ion channels localized in the brain, including the NMDA-glutamate receptor. This has led to the hypothesis that effects on ion channel function may contribute to toluene neurotoxicity, CNS depressive behavior, and altered visual evoked potentials observed in animals and humans. However, this hypothesis has not been tested in vivo. The present experiment examines potential toluene targets in whole animals by measuring visual evoked potentials (VEPs) during toluene exposure and challenging with a drug that antagonizes toluene's action at the NMDA-glutamate receptor. Therefore the goal of this study was to verify changes in VEPs during toluene exposure and demonstrate that toluene inhibits NMDA-glutamate receptor mediated functions in visual evoked potentials elicited from rats. One week prior to testing, recording electrodes were implanted in the rat skull above left visual cortex. Awake, restrained rats were presented with an onset/offset pattern containing a spatial frequency of 0.16 cpd, temporal frequency of 4.55 Hz, with a 60 percent contrast between bars. Baseline VEPs were recorded and rats were injected with either saline or NMDA (10 mg/kg, i.p.). Ten minutes after injection animals were exposed to air or toluene (2000 ppm). VEP amplitudes were calculated for 2X stimulus frequency (F2) for each rat. Thirty minutes after injection of NMDA or saline, NMDA/air (n=5) treatments decreased F2 by 15 percent, saline/toluene (n=6) decreased F2 by 42 percent and toluene/NMDA (n=6) decreased F2 amplitude by 63 percent, contrary to expectations. These results indicate an unanticipated, additive effect of toluene and NMDA on decreasing F2 amplitude. Thus, there appears to be an interaction between NMDA and toluene in the visual system. (This abstract does not reflect EPA policy)