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ToxSci Advance Access published online on April 15, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg072
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received December 18, 2002; accepted February 17, 2003
© 2003 Society of Toxicology

Neurotoxicology

Disassociation of Carbon Disulfide (CS2)-Induced Depression of Flash Evoked Potential (FEP) Peak N166 Amplitude and Norepinephrine (NE) Levels

Jaimie E. Graff 1 David W. Herr 1*

1 Neurotoxicology Division, MD-74B, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709 USA

* To whom correspondence should be addressed. E-mail: Herr.david{at}epamail.epa.gov.


  Abstract

Exposure to organic solvents frequently causes functional impairment of the central nervous system (CNS). One method to examine the effects of solvent exposure on visual function is flash evoked potentials (FEPs). Greater knowledge of the role of various neurotransmitters in generating FEP peaks would be beneficial for understanding the basis of neurotoxicant-induced changes. FEP peak N166 is influenced by the psychological construct of arousal, which in turn is believed to be influenced by the function of neurons containing norepinephrine (NE). Because of its known effects on both NE and FEPs, we utilized carbon disulfide (CS2) as a means to examine the possible role of NE in modulating the amplitude of FEP peaks N36 and N166. Our hypothesis was that CS2-induced alterations in cortical NE levels would be correlated with changes in FEP peak N36 and N166 amplitudes. Adult male Long Evans rats were implanted with electrodes over their visual cortex and allowed to recover. To develop peak N166, FEPs were recorded for two days prior to dosing. On the third day, FEPs were recorded prior to dosing and one group of animals was sacrificed to serve as pre-treatment controls. The remaining animals were dosed ip with 0 (corn oil vehicle; 2 ml/kg), 100, 200, or 400 mg/kg CS2. The treated animals were retested at 1, 4, 8, or 24 h after dosing, immediately sacrificed, and samples of the cortex, cerebellum, striatum, and brainstem were frozen for HPLC analysis of monoamine levels. Treatment with CS2 decreased peak N166 amplitude at 1 h, and peak N36 amplitude was depressed at 4 h, relative to the subject's pre-treatment values. Peak latencies were increased, and colonic temperature was decreased, by treatment with CS2. Exposure to CS2 depressed NE levels in the cortex, brainstem and cerebellum 4 h after treatment. Conversely at 4 h, levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid were increased in the brainstem and cerebellum, and levels of the DA metabolite homovanillic acid were increased in the brainstem. Levels of serotonin were unaffected by CS2 treatment. There was a slight increase in striatal levels of the serotonin metabolite 5-hydroxyindole acetic acid at all times after treatment with CS2. There was no apparent association between the decreases in NE levels and the reductions in amplitudes for peaks N36 and N166. The neurochemical mechanism for CS2-induced reductions in FEP peak amplitudes remains to be determined.

carbon disulfide, flash evoked potential (FEP), norepinephrine .


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